Dr. Spence’s Research

Genetic risk prediction of new atrial fibrillation after cardiac surgery

Background: Postoperative atrial fibrillation (POAF) occurs in up to 50% of cardiac surgery patients. Clinicians struggle to predict who will get POAF, to mitigate its adverse effects and to identify patients who require long-term. Polygenic risk scores combine information from thousands of genetic variants. For patients with POAF after cardiac surgery, polygenic risk scores could help differentiate patients with transient and reversible AF from those with persistent or paroxysmal AF. Moreover, these risk scores may also identify high risk patients who could benefit from AF prophylaxis in the pre-, intra- and early post-operative settings.

Objective: We will compare polygenic risk scores between those with: 1) new POAF following surgery, 2) a known history of AF and 3) no history of AF. We will also test whether polygenic risk scores for AF will predict POAF better than clinical risk scores and whether, among patients with POAF, higher polygenic risk scores for AF are associated with higher rates of AF recurrence in the year following surgery.

Methods: VISION-Cardiac Surgery Biobank obtained blood samples from 3785 patients undergoing cardiac surgery. We will estimate genetic risk using minimal reference sets of single nucleotide polymorphisms, calculate genetic risk scores for AF for each participant using LDpred2, and compare polygenic risk scores of patients with POAF to patients with and without a history of AF. We will assess the ability of polygenic risk scores to predict POAF as compared to traditional risk scores and the association between polygenic risk scores and AF recurrence in patients with POAF.

Expected Outcomes: Patients with new POAF after cardiac surgery will have higher polygenic risk scores for AF than patients without AF but lower scores than patients with a history of AF and that these scores better predict POAF than clinical risk scores. Higher polygenic risk scores will be associated with a higher rate of AF recurrence.

Related Publications

Protein alterations in patients with delirium after cardiac surgery: An exploratory case-control sub-study of the VISION Cardiac Surgery Biobank
Jessica Spence, et al

Delirium is an acute state of confusion associated with adverse postoperative outcomes. To agnostically discover novel biomarkers of delirium, researchers conducted a case-control sub-study using the VISION-Cardiac Surgery biobank. The objective was to identify candidate biomarkers to investigate in future studies. The authors used a sample of 30 patients with delirium on postoperative day 1, and matched them to 30 controls associated by age, sex, ethnicity, center and cardiopulmonary bypass time.  Protein expression was compared between cases and controls using a paired t-test; significantly different biomarkers based on a False Discovery Rate (FDR)-adjusted p-value<0.05 were reported.  Findings show 26 biomarkers significantly associated with delirium, all novel except for IL-8.  However, the results did not identify an association between delirium and recognized neuro-inflammatory proteins and markers of brain injury, which supports using biomarkers to differentiate between delirium and other neurological conditions.  While exploratory, the findings support using biomarkers to diagnose postoperative delirium and validate using agnostic screens to identify potential delirium biomarkers.