Title: New-onset atrial fibrillation in critically ill patients: risk factors and outcomes
Funder: Department of Health and Social Care

Abstract: Background New-onset atrial fibrillation (NOAF) is defined as AF (atrial fibrillation) occurring in a patient with no known history of chronic or paroxysmal AF [2]. NOAF is the most common arrhythmia in critically ill patients [3]. NOAF occurs in 4.5-11% of patients [4, 5] treated on an ICU, increasing to 23% of those patients with septic shock [6]. Current understanding of NOAF precipitants in ICU patients is limited. We know little about the haemodynamic or end-organ effects of NOAF in patients in an ICU. Studies investigating the survival impact of NOAF in critically ill patients are limited by size or methodology. We do not know whether different NOAF durations affect outcome. Aims and objectives My research aim is to increase the understanding of which patients on an ICU get NOAF and how it affects them. The objectives are to: Identify modifiable and non-modifiable risk factors for NOAF in patients treated in an ICU. Develop and validate a NOAF prediction model. Describe the immediate haemodynamic and end-organ effects of NOAF in patients treated on an ICU. Determine whether NOAF is an independent predictor of ICU, in-hospital or long-term mortality, identify the magnitude of any impact and how NOAF duration affects outcomes.Methods I will use four large databases containing the electronic records of patients admitted to ICUs. Together these contain data relating to almost 300,000 patients treated on ICUs in the UK and the USA. I will identify adult patients who developed NOAF. I will analyse modifiable and non-modifiable risk factors for NOAF. Along with learning standard statistical techniques, I will also learn machine learning techniques to explore complex non-linear associations between predictor variables and NOAF. I will use these predictors to develop a NOAF prediction model. The different databases will allow derivation and validation to occur in truly separate data. I will describe the effect of NOAF on patients' physiological measurements and markers of organ failure using signal averaging techniques. I will develop skills in using multivariate logistic regression and survival analysis, including causal inference methods. Using these techniques I will investigate the mortality associated with NOAF occurrence and NOAF duration. Anticipated impact and dissemination My proposed work will be the largest assessment of risk factors and outcomes of NOAF in patients treated on a general ICU. It will be the first to analyse international data to ensure worldwide applicability. This will be the first study to analyse modifiable risk factors for NOAF in detail. Understanding these factors underpins future work to prevent NOAF in these patients. Properly understanding the haemodynamic, end-organ and mortality effects are key to future work aiming to improve outcomes. I will present my work at the annual meetings of the UK and European Intensive Care Societies. I will publish my work in peer-reviewed open-access journals in the ICU and general medical fields. I will maximise patient and public awareness with the help of the 'ICUsteps' charity, our local Oxford ICU patient forum, and the UK Intensive Care Society's patient group.

Lay abstract: What is Atrial Fibrillation? Atrial fibrillation (AF) is a problem with the heart's electrical system that causes an irregular heartbeat. It makes the heart less efficient at pumping blood around the body and can result in a very fast heart rate. Atrial fibrillation also increases the risk of blood clots forming in the heart. These can cause strokes if they travel to the brain. AF in the community is different to AF on the intensive care unit (ICU) AF is the most common electrical heart problem in the UK. Why people develop AF outside hospital is well understood, as are the problems that AF causes in these people. AF can also start when a person becomes very unwell. Around 10% of patients treated on an intensive care unit (ICU) will develop AF for the first time during their ICU stay. This is called 'new-onset AF'. Each year roughly 17,000 people being treated in ICUs in the UK will develop this problem. We do not understand what causes new-onset AF (NOAF) on the ICU NOAF in patients treated on an ICU may be triggered by many different factors. These may include: The normal body reactions to infection and injury. Altered levels of salts in the blood (electrolytes). Certain treatments or procedures commonly used in ICUs, such as large drip lines in the neck.We need to know how big a risk ICU-related NOAF is to patientsWe do not have a clear understanding of all the long-term risks associated with NOAF developing in a patient treated in an ICU. This is because studies in this area are either small or based on limited information. In addition, we know very little about how things like heart rate and blood pressure are affected when NOAF starts in a patient treated on an ICU, and how this affects other organs in the body. NOAF on the ICU may be associated with short and long-term problems Limited studies suggest that NOAF may make patients treated on ICUs more unstable and more likely to die whilst on ICU. Even patients that have AF for a short time whilst on the ICU seem to be at higher risk of dying or having a stroke in hospital. NOAF starting while a patient is in an ICU may also cause long-term problems. These patients may end up with permanent AF. They may also be more likely to die following discharge from hospital. However, larger and more detailed studies are required to work out these risks in detail. My research will help answer these questions My research will use four large databases containing anonymised clinical records of patients treated in ICUs in the UK and America. Studying these databases will allow me to: Understand what makes patients likely to develop NOAF and whether some of the risks are avoidable. Use these risks to predict who will develop NOAF on an ICU. Investigate how NOAF on the ICU affects patients' blood pressure and organ function. Accurately estimate the effect of NOAF on survival on ICU, in the hospital after discharge from ICU and after discharge home. This will include the impact of NOAF duration and whether it persists to ICU discharge.This work will, for the first time, identify avoidable risk factors for NOAF and measure its effect on patients' blood pressure and organ function whilst in ICU. Understanding what triggers NOAF will help clinicians prevent this important condition. Properly understanding future risks is essential to decide on appropriate screening and treatment. Both are needed to improve outcomes in this vulnerable group of patients treated on ICUs.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: CARDIOVASCULAR