Objective: To present a novel method that uses an epigenetic fingerprint to measure changes in plasma concentrations of cardiac-specific cell-free DNA (CS-cfDNA) as a marker of myocardial cell death.
Methods: This prospective, analytic, observational comparative study included patients with heart disease or multiple risk factors for heart disease undergoing major noncardiac, mostly vascular surgery, requiring an arterial-line, and at least 24 h hospitalization in the post anaesthesia care unit or critical care unit after surgery. Blood samples were collected at least four times per patient to measure troponin-T (via high-sensitivity troponin-T test) and CS-cfDNA pre- and postoperatively.
Background: Vascular endothelial cells (VECs) are an essential component of each tissue, contribute to multiple pathologies, and are targeted by important drugs. Yet, there is a shortage of biomarkers to assess VEC turnover.
Methods: To develop DNA methylation-based liquid biopsies for VECs, we determined the methylome of VECs isolated from freshly dissociated human tissues.
We present a patient who was admitted for carotid endarterectomy due to tight carotid stenosis and recent amaurosis fugax. His medical history included significant coronary artery disease with stable angina pectoris, hypertension with wide pulse pressure, chronic renal failure, and anemia. During preparation for surgery, the patient developed type 2 myocardial infarction with prolonged chest pain, ST depressions on electrocardiogram, and significant troponin elevations.
View Article and Find Full Text PDFMethylation patterns of circulating cell-free DNA (cfDNA) contain rich information about recent cell death events in the body. Here, we present an approach for unbiased determination of the tissue origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types. The method is validated using in silico simulations as well as in vitro mixes of DNA from different tissue sources at known proportions.
View Article and Find Full Text PDFLiver damage is typically inferred from serum measurements of cytoplasmic liver enzymes. DNA molecules released from dying hepatocytes are an alternative biomarker, unexplored so far, potentially allowing for quantitative assessment of liver cell death. Here we describe a method for detecting acute hepatocyte death, based on quantification of circulating, cell-free DNA (cfDNA) fragments carrying hepatocyte-specific methylation patterns.
View Article and Find Full Text PDFDetection of cardiomyocyte death is crucial for the diagnosis and treatment of heart disease. Here we use comparative methylome analysis to identify genomic loci that are unmethylated specifically in cardiomyocytes, and develop these as biomarkers to quantify cardiomyocyte DNA in circulating cell-free DNA (cfDNA) derived from dying cells. Plasma of healthy individuals contains essentially no cardiomyocyte cfDNA, consistent with minimal cardiac turnover.
View Article and Find Full Text PDFBackground: Myocardial dysfunction may contribute to the haemodynamic instability which accompanies sepsis, and may result in circulatory failure. There is no association between systolic dysfunction (SD) and mortality in septic patients and there is conflicting evidence regarding the effects of diastolic dysfunction (DD) on mortality in septic patients.
Methods: We conducted a systematic review and meta-analysis to investigate DD and mortality in septic patients.
Background: In vitro studies suggested that circulating inflammatory cytokines cause septic myocardial dysfunction. However, no in vivo clinical study has investigated whether serum inflammatory cytokine concentrations correlate with septic myocardial dysfunction.
Methods: Repeated echocardiograms and concurrent serum inflammatory cytokines (IL-1β, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α, and monocyte chemoattractant protein-1) and cardiac biomarkers (high-sensitivity [hs] troponin-T and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) were examined in 105 patients with severe sepsis and septic shock.
Objective: Serum troponin concentrations predict mortality in almost every clinical setting they have been examined, including sepsis. However, the causes for troponin elevations in sepsis are poorly understood. We hypothesized that detailed investigation of myocardial dysfunction by echocardiography can provide insight into the possible causes of troponin elevation and its association with mortality in sepsis.
View Article and Find Full Text PDFAims: Systolic dysfunction in septic shock is well recognized and, paradoxically, predicts better outcome. In contrast, diastolic dysfunction is often ignored and its role in determining early mortality from sepsis has not been adequately investigated.
Methods And Results: A cohort of 262 intensive care unit patients with severe sepsis or septic shock underwent two echocardiography examinations early in the course of their disease.
Curr Opin Crit Care
August 2011
Purpose Of Review: Three topics are at the forefront of the investigation and treatment of patients with coronary artery disease (CAD) undergoing major noncardiac surgery: prophylactic perioperative beta-blockade (PPBB), prophylactic statins and prophylactic preoperative coronary revascularization (PCR). The purpose of the review is to summarize the investigational efforts in each one of these fields and to provide a subjective evaluation as to their impact on perioperative patient care.
Recent Findings: The data on PPBB are still controversial.
Background: There is uncertainty regarding the prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurements after noncardiac surgery.
Methods: The current study undertook a systematic review and meta-analysis. The study used six search strategies and included noncardiac surgery studies that provided data from a multivariable analysis assessing whether a postoperative troponin or creatine kinase muscle and brain isoenzyme measurement was an independent predictor of mortality or a major cardiovascular event.
Background: In a previous study it has been shown that a long-term survival score (LTSS), composed of Lee's Revised Cardiac Risk Index (RCRI) criteria supplemented by age, preoperative electrocardiography (EKG) features, and all types of diabetes to the RCRI criteria, predicts long-term (3-15 years) survival after major vascular surgery. The present study aimed to investigate the performance of LTSS in predicting earlier survival (3 months-3 years) as compared with the RCRI.
Methods: Data from 921 consecutive patients undergoing major vascular surgery (624 patients at Hadassah Medical Center [HMC] and 296 patients in Beth Israel Deaconess Medical Center [BIDMC]) were collected retrospectively.
Background: Thoracoabdominal aortic aneurysm repair requires complex surgery. Clamping of the descending aorta during the operation results in organ malperfusion, ischemia, and in some cases, irreversible end-organ damage and death. Several methods for organ preservation during the operation evolved, resulting in decreased post-operative organ malfunction.
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