Juhani M Knuuti

Turku University Hospital · Turku PET Centre

Background: New Block-Sequential-Regularized-Expectation-Maximization (BSREM) image reconstruction technique has been introduced for clinical use mainly for oncologic use. Accurate and quantitative image reconstruction is essential in myocardial perfusion imaging with positron emission tomography (PET) as it utilizes absolute quantitation of myoca...

Aims Data on the warranty period of coronary computed tomography angiography (CTA) and combined coronary CTA/positron emission tomography (PET) are scarce. The present study aimed to determine the event-free (warranty) period after coronary CTA and the potential additional value of PET. Method and results Patients with suspected but not previously...

Objective To investigate the associations of sedentary time, physical activity, and cardiorespiratory fitness with skeletal muscle glucose uptake (GU). Methods Sedentary time and physical activity were measured with accelerometers, and VO2max with cycle ergometry in 44 sedentary adults with metabolic syndrome. Thigh muscle GU was determined with [...

Background Substantial differences exist between different guideline‐recommended pretest probability (PTP) models for the detection of obstructive coronary artery disease (CAD). This study was performed to study the performance of the 2021 American Heart Association/American College of Cardiology (AHA/ACC) guideline‐recommended PTP (AHA/ACC‐PTP) mo...

Background: The prospective, multicentre EURECA registry assessed the use of imaging and adoption of the European Society of Cardiology (ESC) Guidelines (GL) in patients with chronic coronary syndromes (CCS). Methods: Between May 2019 and March 2020, 5156 patients were recruited in 73 centres from 24 ESC member countries. The adoption of GL reco...

Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventric...

Some studies have indicated that the use of 2D-Speckle tracking echocardiography (2DSTE) aids in predicting recovery of myocardial contractile function after revascularization in patients with chronic ischemic left ventricular (LV) dysfunction or acute myocardial infarction (MI). The purpose of this meta-analysis was to evaluate the diagnostic accu...

Background: This study examined whether hemoglobin (Hb) and white blood cell count (WBC) associate with body adiposity and other cardiometabolic risk factors, as well as accelerometer-measured sedentary behavior (SB) and physical activity (PA), when adjusted for body mass index (BMI). Methods: The cross-sectional analysis included 144 participan...

Coronary plaque composition may play an important role in the induction of myocardial ischemia. Our objective was to further clarify the relation between coronary plaque composition and myocardial ischemia in patients with chest pain symptoms. The study population consisted of 103 patients who presented to the outpatient clinic or emergency departm...

Background In patients with suspected obstructive coronary artery disease (CAD), the risk factor–weighted clinical likelihood (RF-CL) model and the coronary artery calcium score–weighted clinical likelihood (CACS-CL) model improves the identification of obstructive CAD compared with basic pretest probability (PTP) models. Objectives The aim of thi...

Background Additional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models to predict hemodynamically obstructive CAD. Methods and results Symptomatic patients with suspected CAD who underwent coronary artery calcium scoring (CAC...

The aim of this study was to investigate the associations between liver fat content (LFC), sedentary behaviour (SB), physical activity (PA), fitness, diet, body composition, and cardiometabolic risk factors in adults with metabolic syndrome. A total of 44 sedentary adults (mean age 58 [SD 7] years; 25 women) with overweight or obesity participated....

Objective: High-density lipoprotein (HDL) is a heterogeneous group of subpopulations differing in protein/lipid composition and in their anti-atherogenic function. There is a lack of assays that can target the functionality of HDL particles related to atherosclerosis. The objective of this study was to construct two-site apolipoprotein A-I (apoA-I...

Introduction Mannose receptor (CD206) is primarily expressed on the surface of alternatively activated macrophages that are involved in resolution of inflammation after myocardial injury [1]. The purpose of this study was to evaluate mannose receptor targeting positron emission tomography (PET) tracer Al[18F]F-NOTA-DCM consisting of dextran backbon...

Background Endothelial wall shear stress (ESS) is a biomechanical force which plays a key role in the formation and evolution of atherosclerotic lesions. Purpose This study aims to evaluate ESS in coronary arteries without atherosclerosis, and to assess various factors affecting ESS values. Methods Coronary computed tomography angiography (CCTA)...

Background Normal coronary computed tomography angiography (CTA) and positron emission tomography (PET) are associated with an excellent prognosis. Hitherto, data on the warranty period of normal coronary CTA and normal myocardial blood flow (MBF) by PET are scarce. Purpose To determine the event-free period after normal coronary CTA and PET resul...

Background Computed Tomography Coronary Angiography (CTCA) is an effective non-invasive imaging modality for anatomo-functional assessment of coronary artery disease (CAD). Radiomics features have been used for diagnosis or outcome prediction, however, their potential value for characterizing flow limiting coronary lesions has not been explored. P...

Background Congenic leptin receptor deficient rat generated by introgression of the Koletsky leptin receptor mutation into BioBreeding Diabetes Resistant rat (BBDR.lepr−/−) is a novel animal model combining obesity, systemic insulin resistance and diabetes. Systemic insulin resistance is associated with reduced myocardial glucose utilization, but i...

Background Coronary flow capacity (CFC) is a cross-modality framework integrating hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) to quantify the physiological impact of coronary atherosclerotic disease on vasodilator capacity. Purpose This study explores the prognostic value of CFC derived from [15O]H2O positron emission to...

Background 68Ga-NODAGA-RGD is a positron emission tomography (PET) tracer targeting αvβ3 integrin that is upregulated during angiogenesis. αvβ3 integrin expression increases early after acute myocardial infarction (AMI), and has been proposed as a marker of myocardial repair. Purpose We prospectively evaluated the uptake of 68Ga-NODAGA-RGD and its...

Background In patients with suspected obstructive coronary artery disease (CAD) and a high pre-test probability, myocardial perfusion imaging (MPI) or referral for invasive coronary angiography (ICA) are viable diagnostic strategies. The present study compared the diagnostic performance of quantitative flow ratio (QFR) and MPI by single-photon emis...

Background High-sensitivity (hs) assays for the measurement of cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are now used widely for the diagnosis of myocardial infarction. However, it is also increasingly apparent that troponin concentrations well below the thresholds used in acute coronary syndromes may provide diagnostic and prognostic...

Background Previous studies have demonstrated that MMP-9 may be a predictor of atherosclerotic plaque instability and future adverse cardiovascular events, but longitudinal data on the association between MMP9 and coronary disease progression are lacking. Purpose This study is aimed at investigating whether MMP9 is associated with atherosclerotic...

Background Coronary CT angiography (CTA) combined with myocardial perfusion imaging accurately detects both non-obstructive and obstructive coronary artery disease (CAD). Lipid-lowering therapy is known to effectively reduce cardiovascular events, but the impact of non-invasive imaging findings on the usage of lipid-lowering therapy remains largely...

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular events. Although the association between NAFLD and aortic valve sclerosis has been described, the prevalence and prognostic implications of NAFLD among patients with severe aortic stenosis (AS) have not been described. In addition, the effect of the pres...

Aims Coronary atherosclerosis with a large necrotic core has been postulated to reduce the vasodilatory capacity of vascular tissue. In the present analysis, we explored whether total plaque volume and necrotic core volume on coronary computed tomography angiography (CCTA) are independently associated with myocardial ischaemia on positron emission...

Background and aims MMP-9 is a predictor of atherosclerotic plaque instability and adverse cardiovascular events, but longitudinal data on the association between MMP9 and coronary disease progression are lacking. This study is aimed at investigating whether MMP9 is associated with atherosclerotic plaque progression and the related molecular basis...

Worsening heart failure (HF), defined as hospitalization for worsening signs and symptoms of HF or the need for urgent intravenous diuretics, is often considered a surrogate of poor prognosis in clinical trials. However, data on the prognostic implications of worsening HF in patients with HF and reduced ejection fraction is limited. Patients who ha...

Pericoronary adipose tissue (PCAT) attenuation, derived from coronary computed tomography angiography (CCTA), is associated with coronary artery inflammation. Values for PCAT attenuation in men and women without atherosclerosis on CCTA are lacking. The aim of the current study was to assess the mean PCAT attenuation in individuals without coronary...

Aims The diagnostic performance of non-invasive imaging in patients with prior coronary artery disease (CAD) has not been tested in prospective head-to-head comparative studies. The aim of this study was to compare the diagnostic performance of qualitative single-photon emission computed tomography (SPECT), quantitative positron emission tomography...

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Commission in the H2020 program: Project SMARTool, “Simulation Modeling of coronary ARTery disease: a tool for clinical decision support—SMARTool” Background and aims The coexistence of elevated plasma triglycerides (TG) and low high-de...

Reduced left ventricular (LV) systolic function is associated with worse prognosis in patients with severe aortic stenosis (AS) treated with transcatheter aortic valve implantation (TAVI). We aimed to examine the changes in left ventricular ejection fraction (LVEF) after TAVI among patients with varying baseline LVEF. Moreover, variables associated...

Aims Evolving evidence suggests that endothelial wall shear stress (ESS) plays a crucial role in the rupture and progression of coronary plaques by triggering biological signalling pathways. We aimed to investigate the patterns of ESS across coronary lesions from non-invasive imaging with coronary computed tomography angiography (CCTA), and to defi...

Patients with diabetes mellitus (DM) may show diffuse coronary artery atherosclerosis on coronary computed tomography angiography (CTA). The present study aimed at quantification of atherosclerotic plaque with CTA and its association with myocardial ischemia on positron emission tomography (PET) in DM patients. Of 922 symptomatic outpatients withou...

The aims of pharmacological management of patients with chronic coronary syndrome (CCS) are to reduce angina symptoms and exercise-induced ischaemia, and to prevent cardiovascular events.¹ Optimal treatment can be defined as the treatment that satisfactorily controls symptoms and prevents cardiac events associated with CCS, with maximal patient adh...

Purpose: Some studies have indicated that the use of 2D-Speckle tracking echocardiography (2DSTE) aids in predicting recovery of myocardial contractile function after revascularization in patients with chronic ischemic left ventricular (LV) dysfunction or acute myocardial infarction (MI). The purpose of this meta-analysis was to evaluate the diagno...

Women with severe aortic stenosis (AS) have better long-term prognosis after transcatheter aortic valve implantation (TAVI) compared to men. Whether this is caused by sex-related differences in left ventricular (LV) reverse remodeling after TAVI is unknown. Patients with severe AS who underwent transfemoral TAVI between 2007 and 2018 were selected....

Purpose of Review As machine learning-based artificial intelligence (AI) continues to revolutionize the way in which we analyze data, the field of nuclear cardiology provides fertile ground for the implementation of these complex analytics. This review summarizes and discusses the principles regarding nuclear cardiology techniques and AI, and the c...

Objectives The aim was to investigate if reducing sedentary behavior (SB) improves cardiometabolic biomarkers in adults with metabolic syndrome (MetS). Design Randomized controlled trial. Methods Sixty-four sedentary middle-aged adults with MetS were randomized into intervention (INT; n = 33) and control (CON; n = 31) groups. INT was guided to li...

[This corrects the article DOI: 10.3389/fimmu.2022.821423.].

This editorial refers to ‘Vessel-specific plaque features on coronary computed tomography angiography among patients of varying atherosclerotic cardiovascular disease risk’, by A.M. Bax et al.https://doi.org/10.1093/ehjci/jeac029. It is often the case out of practical convention that intuitions on the distribution and progression of a disease in a...

Objectives There is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD). Purpose To determine whether CTA is superior to the Agatston score in the diagnosis of CAD. Methods In total 2452 patients with...

Hypo-attenuated leaflet thickening (HALT) of transcatheter aortic valves is detected on multidetector computed tomography (MDCT) and reflects leaflet thrombosis. Whether HALT affects left ventricular (LV) reverse remodeling, a favorable effect of LV afterload reduction after transcatheter aortic valve implantation (TAVI) is unknown. The aim of this...

The distribution of epicardial adipose tissue (EAT) across the spectrum of heart failure (HF) has yet to be fully elucidated. The present study investigated the distribution of EAT in an HF spectrum and its association with clinical and echocardiographic parameters. A total of 326 patients who underwent contrast-enhanced computed tomography before...

We implemented a two-dimensional convolutional neural network (CNN) for classification of polar maps extracted from Carimas (Turku PET Centre, Finland) software used for myocardial perfusion analysis. 138 polar maps from 15O–H2O stress perfusion study in JPEG format from patients classified as ischemic or non-ischemic based on finding obstructive c...

Therapeutic angiogenesis induced by gene therapy is a promising approach to treat patients suffering from severe coronary artery disease. In small experimental animals, adeno-associated viruses (AAVs) have shown good transduction efficacy and long-term transgene expression in heart muscle and other tissues. However, it has been difficult to achieve...

Background Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and may provoke structural and functional changes in coronary vasculature. The coronary volume to left ventricular mass (V/M) ratio is a new anatomical parameter capable of revealing a potential physiological imbalance between coronary vasculature and myocardial m...

Background Cardiac resynchronization therapy (CRT) candidates often present with significant mitral and tricuspid regurgitation, pulmonary hypertension and right ventricular dysfunction when referred for device implantation. This study investigated the prognostic value of a novel cardiac staging system, based on the extent of cardiac remodeling pri...

Increased glutamine metabolism by macrophages is associated with development of atherosclerotic lesions. Positron emission tomography/computed tomography (PET/CT) with a glutamine analog (2S,4R)-4-18F-fluoroglutamine (18F-FGln) allows quantification of glutamine consumption in vivo. Here, we investigated uptake of 18F-FGln by atherosclerotic lesion...

Purpose Women with severe aortic stenosis (AS) have better long-term prognosis after transcatheter aortic valve implantation (TAVI) compared to men. Whether this is caused by sex-related differences in left ventricular (LV) reverse remodeling after TAVI is unknown. Methods Patients with severe AS who underwent transfemoral TAVI between 2007 and 20...

This editorial refers to ‘Myocardial efficiency in patients with different aetiologies and stages of heart failure’, by K.B. Hansen et al., pp. 328–337. Positron emission tomography (PET) with carbon-11 acetate (¹¹C-acetate) is a non-invasive method for measuring myocardial oxygen consumption.¹ Once taken up by the myocytes, acetate is transformed...

The ⁶⁸ Gallium-labeled 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid conjugated radiolabelled arginine-glycine-aspartic acid peptide ([ ⁶⁸ Ga]Ga-NODAGA-RGD) is a positron emission tomography (PET) tracer binding to cell surface receptor α v β 3 integrin that is upregulated during angiogenesis and inflammation. We studied whether α v β 3...

Background: The NF-E2-related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway has an emerging role in atherosclerosis. Activated by oxidative stress, it is deemed to exert athero-protective effects. We aimed at evaluating the relationships between plasma HO-1, clinical/molecular profiles and coronary disease patterns in patients with chronic coron...

Introduction: Women with severe aortic valve stenosis (AS) have better long-term prognosis after transcatheter aortic valve implantation (TAVI) compared to men. Whether this is caused by sex-related differences in left ventricular (LV) reverse remodeling after TAVI is unknown. Purpose: To examine the interaction between sex and LV reverse remodelin...

Nearly half of all patients with heart failure (HF) have a normal left ventricular (LV) ejection fraction (EF) and the condition is termed heart failure with preserved ejection fraction (HFpEF). It is assumed that in these patients HF is due primarily to LV diastolic dysfunction. The prognosis in HFpEF is almost as severe as in HF with reduced EF (...

Background: Cardiorespiratory fitness (CRF) has been inversely associated with insulin resistance and clustering of cardiometabolic risk factors among overweight and obese individuals. However, most previous studies have scaled CRF by body mass (BM) possibly inflating the association between CRF and cardiometabolic health. We investigated the asso...

Background and aims Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) define a specific lipid profile associated with residual coronary artery disease (CAD) risk independently of total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Aim of the present study was to assess whether TG/HDL-C ratio, cor...

Noise and motion artifacts in Positron emission tomography (PET) scans can interfere in diagnosis and result in inaccurate interpretations. PET gating techniques effectively reduce motion blurring, but at the cost of increasing noise, as only a subset of the data is used to reconstruct the image. Deep convolutional neural networks (DCNNs) could com...

Background The amount of coronary artery calcification is a general marker of coronary atherosclerosis and has been associated with increased risk of adverse cardiac events. On the other hand, calcification of coronary artery plaques has also been considered as a marker of plaque stabilization. Purpose We hypothesized that the fraction of the non-...

Background Women with severe aortic valve stenosis (AS) have better long-term outcomes after transcatheter aortic valve implantation (TAVI) but worse survival after surgical aortic valve replacement compared to men. Whether this is related to sex differences in left ventricular (LV) remodeling is unknown. Purpose To examine sex differences in LV r...

Objectives The association between the subjective experience of pain-related disability (PRD) and device-measured physical activity (PA) and sedentary behavior (SB) in overweight and obese adults is not well known. The aim of this study was to investigate the associations of pain markers with accelerometer-measured SB duration and different intensi...

Aims Women with severe aortic stenosis (AS) have better long-term outcome after transcatheter aortic valve implantation (TAVI) but worse survival after surgical aortic valve replacement compared with men. Whether this is related to sex differences in left ventricular (LV) remodelling is unknown. The aim of this study was to examine the sex differe...

Background and objectives Absence of obstructive coronary artery disease (CAD) in patients with angina is common, but its prognosis debated. We investigated outcomes of such patients to identify predictors of cardiovascular events. Methods We selected 1,014 patients with angina, evidence of myocardial ischemia at the electrocardiogram (ECG) exerci...

Background The aim of the present study was to compare the quantitative flow responses of regadenoson against adenosine using cardiac ¹⁵ O-water PET imaging in patients with suspected or known coronary artery disease (CAD). Methods Hyperemic myocardial blood flow (MBF) after adenosine and regadenoson was compared using correlation and Bland–Altman...

Global left ventricular (LV) myocardial work (MW) indices (GLVMWI) are derived from speckle tracking echocardiographic strain data in combination with non-invasive blood pressure measurements. Changes in global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) after ST-segment elevation myoc...

Coronary computed tomography angiography (CTA) has shown great technological improvements over the last 2 decades. High accuracy of CTA in detecting significant coronary stenosis has promoted CTA as a substitute for conventional invasive coronary angiography in patients with suspected coronary artery disease. In patients with coronary stenosis, CTA...