Antti Saraste

Background and Aims: The long-term prognostic value of a guideline-recommended selective sequential anatomical-functional imaging strategy using coronary computed tomography angiography (CCTA) followed by quantitative [15O]H2O positron emission tomography (PET) remains uncertain. We evaluated its long-term prognostic value in patients with first symptoms suggestive of obstructive coronary artery disease (CAD). Methods: In this multicentre European cohort, symptomatic patients first underwent CCTA and were selectively referred to quantitative [15O]H2O PET in case of suspected obstructive stenosis (≥50%). Patients were stratified according to CCTA findings and PET-derived ischaemia (normal CCTA; non-obstructive CAD on CCTA; obstructive CAD on CCTA without ischaemia; obstructive CAD on CCTA with ischaemia). The primary endpoint was a composite of all-cause mortality, non-fatal myocardial infarction (MI), and hospitalization for unstable angina (UA). Adjusted hazard ratios (aHRs) were calculated. Results: Among 3,918 patients (61.0±9.8 years; 54.3% female) with a median follow-up of 5.1 [3.8-8.0] years, 278 (7.1%) experienced the primary endpoint. aHRs increased stepwise across CCTA-PET categories. Compared to normal CCTA, non-obstructive CAD and obstructive CAD without ischaemia were associated with a higher risk of the combined primary endpoint (aHR 1.89, [95%CI: 1.23-2.91], p=0.004; aHR 3.20, [95%CI: 1.95-5.25], p<0.001). Among patients with obstructive CAD on CCTA, PET-derived ischaemia further increased the risk of the primary endpoint (aHR 1.55, [95%CI: 1.05-2.30]; p=0.029), but not when excluding UA from the composite endpoint (aHR 1.37, [95%CI 0.90-2.07]; p=0.141). PET-derived ischaemia primarily predicted events within the first year, while obstructive CCTA findings remained associated with long-term hard outcomes. Conclusions: A sequential strategy combining CCTA and quantitative [15O]H2O PET provides robust and incremental long-term risk stratification. While PET-derived ischaemia refines prediction of short-term and symptom-driven events, CCTA-derived CAD remains the principal determinant of long-term hard outcomes.

Peripheral physiological processes contribute to emotions; however, the extent of the influence of internal signals to subjective emotional experiences remains a subject of debate. Methods: Here we investigated the bodily sensations induced by pharmacological stimulation with adenosine, a potent vasodilator that does not cross the blood-brain barrier, and how these sensations are translated into emotional experiences in 193 patients (94 males, 99 females; mean age 62.6 ± 9.2 years) undergoing pharmacological cardiac stress testing as a part of their clinical assessment for suspected obstructive coronary artery disease. We characterized the subjective experiences induced by adenosine using topographical bodily maps and Likert-rating scales of 16 somatic sensations and 16 emotions. Results: Adenosine induced strong and consistent bodily sensations related to dyspnea, chest pain, tachycardia, feelings of warmth and tension in the body. The induced sensations were topographically distinct, with pain and pressure concentrated in the chest, warmth distributed across the upper body, and weakness localized to the torso. These sensations were accompanied by a significant increase in negative emotions, such as anxiety, fear, restlessness, panic, and a decrease in positive emotions of happiness, joy, and calmness. Peak heart rate response predicted the intensity of most bodily and emotional responses. Patients diagnosed with myocardial ischemia did not show heightened sensitivity to adenosine-induced bodily sensations compared to non-ischemic patients, despite exhibiting a blunted tachycardiac reflex. Conclusion: These findings show that peripheral physiological activation alone is sufficient to drive subjective emotional experiences, providing causal evidence for the embodied nature of emotions.

Background: Increased epicardial adipose tissue volume (EATV) is a potentially important risk marker for coronary artery disease (CAD) available from cardiac computed tomography (CT) images. Sex-differences and effects of age and body size on EATV have been insufficiently explored, and no reliable reference values exist. Consequently, EATV has yet to find its deserved use in clinical practice. Objectives: To define normal values by sex and age, the best normalization procedure for EATV to neutralize effects of body-size, explore the relationship between normalized EATV and cardiac risk, and propose a clinically meaningful cut-off. Methods: AI-based automated EATV data from the general population (n=25,155) and a clinical cohort (n=2,482) with suspected CAD was normalized to height, BSA and heart volumes. Correlation between EATV and EAT attenuation was tested with Spearman?s rank correlation and linear regression to find the optimal normalization. Normalized EATV was compared to high-risk by SCORE2 and obstructive CAD in the population cohort. A cut-off including 95% of cases with obstructive CAD was defined in the general population and tested in the clinical cohort. Results: EATV varied with sex and age across cohorts. Normalization of EATV to total heart volume (EATVh) was superior by all metrics and neutralized the effects of sex. High-risk by SCORE2 and the prevalence of obstructive CAD increased over quartiles of EATVh in the population cohort, and significantly higher EATVh was seen with obstructive CAD in both cohorts. A cut-off of 0.1 in EATVh had a negative predictive value for obstructive CAD of 97.1% in the general population and 88.9% in the clinical cohort. Conclusions: EATV varies considerably with sex, age and body size. Normalization to heart volume outperformed other procedures, and EATVh is a useful marker of obstructive CAD in both the general population and symptomatic patients.

BACKGROUND: We hypothesized that quantification of coronary atherosclerotic plaque burden by artificial intelligence-guided quantitative computed tomography can identify patients who derive outcome benefit from lipid-lowering medication (LLM). METHODS: In this observational cohort study, consecutive symptomatic patients undergoing coronary computed tomography angiography for suspected coronary artery disease (CAD) were assessed for percent atheroma volume (PAV) by artificial intelligence-guided quantitative computed tomography. The use of LLM was assessed based on drug purchase registry data within 6 months after coronary computed tomography angiography. Patients were followed for the composite of death, myocardial infarction, and unstable angina for a median of 6.9 years. RESULTS: Among 2269 patients (median age, 63 years; 42% men), 1261 (56%) patients used LLM after coronary computed tomography angiography, and 255 (11%) experienced the composite end point during follow-up. The median PAV was 6.6% among users and 1.4% among nonusers of LLM ( P 5% (annual event rate, 2.62% versus 4.14%; adjusted P =0.002), even in the absence of obstructive CAD, but not among the 1359 patients with PAV ≤5% (annual event rate, 0.94% versus 0.65%; adjusted P =0.717). An adjusted Cox regression analysis, including interaction between PAV and LLM, suggested a PAV threshold between 4% and 10% for gaining prognostic benefit from LLM. CONCLUSIONS: In symptomatic patients with suspected CAD, LLM after coronary computed tomography angiography was associated with a lower rate of adverse events during long-term follow-up among those with PAV >5%, even in the absence of obstructive CAD. The quantification of coronary atherosclerotic plaque burden is a potential marker to guide preventive lipid-lowering therapy.

Aims: Second-line functional imaging is recommended following an abnormal coronary computed tomography angiography (CCTA). However, evidence guiding the choice of imaging modality is limited. We assessed the diagnostic performance of second-line functional imaging using different invasive reference standards. Methods and results: We conducted an individual patient-data meta-analysis of seven prospective diagnostic studies including 1410 patients (mean age 62 ± 8.1 years, 67% male) with abnormal CCTA [≥50% diameter stenosis (DS)], who underwent second-line functional imaging tests (dobutamine stress ECHO, SPECT, CMR, and/or PET) followed by invasive angiography with fractional flow reserve (FFR) and quantitative coronary angiography (QCA). Haemodynamically obstructive coronary artery disease (CAD) was defined as invasive FFR ≤0.80 or >90% visual DS; anatomically severe CAD as ≥70% DS by QCA. Pooled and per test, 904/1906 (47.2%) functional imaging tests had haemodynamically obstructive CAD, and 504/1906 (26.3%) functional imaging tests had anatomically severe CAD. In total, 730/1906 (38.3%) functional imaging tests were abnormal. Pooled sensitivity and specificity were 63% and 84% for haemodynamically obstructive CAD, and 81% and 77% for anatomically severe CAD. Findings were generally stable across sex and age. More advanced second-line functional imaging tests showed higher sensitivities, but lower specificities compared to less advanced techniques. Conclusion: Second-line functional imaging after an abnormal CCTA enables identification of patients with anatomically severe CAD. In contrast, moderate stenoses (<70% DS) with FFR ≤0.80 do not consistently result in myocardial ischaemia detectable by functional imaging tests. Substantial diagnostic accuracy differences were found between non-invasive diagnostic test which need further investigation. Clinical trial identifiers: NCT02264717, NCT03481712, NCT04707859, NCT01521468