Thomas S. Kristensen

Left Atrial Function and Mortality in Patients With NSTEMI: An MDCT Study

OBJECTIVES We sought to test the hypothesis that measures of left atrial (LA) function are independent predictors of mortality in patients with acute myocardial infarction. BACKGROUND Left atrial maximal volume (LAmax) is known to predict mortality in patients with acute myocardial infarction. In a previous pilot study, however, we found that LA function in terms of fractional change and left atrial ejection fraction (LAEF) assessed by multidetector computed tomography (MDCT) is more closely related to clinical heart failure than LAmax. METHODS We prospectively included 384 patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) who underwent retrospectively gated, 64-slice MDCT coronary angiography and subsequent measurements of LA size and function. All patients were treated according to the current guidelines based on invasive coronary angiography. Patients were followed for a minimum of 2 years. The study endpoint was all-cause mortality. RESULTS The median follow-up time was 36 months (range 10 to 1,551 days). During follow-up, 35 (9%) patients died. Overall, 1- and 2-year survival in the study cohort was 97% and 94%. LA size and mechanical function was obtained in all patients: mean LAmax was 55 ± 11 ml/m(2), LA minimal volume 31 ± 11 ml/m(2), fractional change 45 ± 9%, and LAEF 32 ± 9%. Using a Cox proportional hazards model with adjustments for age, number of diseased coronary vessels, left ventricular ejection fraction (LVEF), and Killip class, both fractional change (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.45 to 0.94) and LAEF (HR: 0.63; 95% CI: 0.44 to 0.91) remained independent predictors of mortality. In contrast to this, LAmax was not significantly associated with an increased risk of mortality in this population. CONCLUSIONS In a low-risk group of patients with NSTEMI, reduced LA function is an independent predictor of mortality and provides prognostic value incremental to that of LAmax.

Liver fat content, non-alcoholic fatty liver disease, and ischaemic heart disease: Mendelian randomization and meta-analysis of 279 013 individuals

Aims In observational studies, non-alcoholic fatty liver disease (NAFLD) is associated with high risk of ischaemic heart disease (IHD). We tested the hypothesis that a high liver fat content or a diagnosis of NAFLD is a causal risk factor for IHD. Methods and results In a cohort study of the Danish general population (n = 94 708/IHD = 10 897), we first tested whether a high liver fat content or a diagnosis of NAFLD was associated observationally with IHD. Subsequently, using Mendelian randomization, we tested whether a genetic variant in the gene encoding the protein patatin-like phospholipase domain containing 3 protein (PNPLA3), I148M (rs738409), a strong and specific cause of high liver fat content and NAFLD, was causally associated with the risk of IHD. We found that the risk of IHD increased stepwise with increasing liver fat content (in quartiles) up to an odds ratio (OR) of 2.41 (1.28-4.51)(P-trend = 0.004). The corresponding OR for IHD in individuals with vs. without NAFLD was 1.65 (1.34-2.04)(P = 3×10-6). PNPLA3 I148M was associated with a stepwise increase in liver fat content of up to 28% in MM vs. II-homozygotes (P-trend = 0.0001) and with ORs of 2.03 (1.52-2.70) for NAFLD (P = 3×10-7), 3.28 (2.37-4.54) for cirrhosis (P = 4×10-12), and 0.95 (0.86-1.04) for IHD (P = 0.46). In agreement, in meta-analysis (N = 279 013/IHD = 71 698), the OR for IHD was 0.98 (0.96-1.00) per M-allele vs. I-allele. The OR for IHD per M-allele higher genetically determined liver fat content was 0.98 (0.94-1.03) vs. an observational estimate of 1.05 (1.02-1.09)(P for comparison = 0.02). Conclusion Despite confirming the known observational association of liver fat content and NAFLD with IHD, lifelong, genetically high liver fat content was not causally associated with risk of IHD. These results suggest that the observational association is due to confounding or reverse causation.

Coronary CT angiography in clinical triage of patients at high risk of coronary artery disease

Abstract Objectives. To test if cardiac computed tomography angiography (CCTA) can be used in the triage of patients at high risk of coronary artery disease. Design. The diagnostic value of 64-detector CCTA was evaluated in 400 patients presenting with non-ST segment elevation myocardial infarction using invasive coronary angiography (ICA) as the reference method. The relation between the severity of disease by CCTA and a combined endpoint of death, re-hospitalization due to new myocardial infarction, or symptom-driven coronary revascularization was assessed. Results. CCTA detects significant (>50%) coronary artery diameter stenosis with a sensitivity, specificity, and positive and negative predictive value of 99%, 81%, 96% and 95%, respectively. CCTA was used to triage patients into guideline defined treatment groups of “no or medical treatment”, “referral to percutaneous coronary intervention” or to “coronary artery bypass graft surgery” and was compared to the index ICA. CCTA correctly triaged patients in 86% of cases. During a median follow-up of 50 months, the presence of an occluded artery by CCTA was associated with adverse outcome. Conclusion. CCTA has high diagnostic and prognostic value in patients with high likelihood of coronary artery disease and could, in theory, be used to triage high risk patients. As many obstacles remain, including logistical and safety issues, our study does not support the use of CCTA as an additional diagnostic test before ICA in an all-comer NSTEMI population.

Data on the quantitative assessment pulmonary ground-glass opacification from coronary computed tomography angiography datasets

We assessed the CT attenuation density of the pulmonary tissue adjacent to the heart in patients with acute non-ST segment elevation myocardial infarction (J.T. Kuhl, T.S. Kristensen, A.F. Thomsen et al., 2016) [1]. This data was related to the level of ground-glass opacification evaluated by a radiologist, and data on the interobserver variability of semi-automated assessment of pulmonary attenuation density was provided.