Juhani M Knuuti

• MD, PhD, Professor
• Turku University Hospital

Aims We sought to evaluate the mechanism of angiotensin‐converting enzyme inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan‐only control group in HFrEF patients. Methods and results The study was a phase IV, prospective, randomized, double‐blind, parallel‐group study in patients with NYHA class II‐III heart failure (HF)...

Objectives Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CA...

Aims To evaluate the incremental value of positron emission tomography (PET) myocardial perfusion imaging (MPI) over coronary computed tomography angiography (CCTA) in predicting short- and long-term outcome using machine learning (ML) approaches. Methods and results A total of 2411 patients with clinically suspected coronary artery disease (CAD)...

Background Vascular adhesion protein-1 (VAP-1) is an adhesion molecule and primary amine oxidase, and Gallium-68-labeled 1,4,7,10-tetraazacyclododecane- N , N ′, N ″, N ‴-tetra-acetic acid conjugated sialic acid-binding immunoglobulin-like lectin 9 motif containing peptide ([ ⁶⁸ Ga]Ga-DOTA-Siglec-9) is a positron emission tomography (PET) tracer ta...

OBJECTIVE To compare cardiac computed tomography (CT) with invasive coronary angiography (ICA) as the initial strategy in patients with diabetes and stable chest pain. RESEARCH DESIGN AND METHODS This prespecified analysis of the multicenter DISCHARGE trial in 16 European countries was performed in patients with stable chest pain and intermediate...

Background: Machine Learning (ML) allows integration of the numerous variables delivered by cardiac PET/CT, while traditional survival analysis can provide explainable prognostic estimates from a restricted number of input variables. We implemented a hybrid ML-and-survival analysis of multimodal PET/CT data to identify patients who developed myoca...

BACKGROUND Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and coronary flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. This study explores the prognostic value of modified CFC derived from [ ¹⁵ O]H 2 O positron emission tomography perfusion imaging...

Background and aims: Clinical management of critical limb-threatening ischemia (CLTI) is focused on prevention and treatment of atherosclerotic arterial occlusions. The role of microvascular pathology in disease progression is still largely unspecified and more importantly not utilized for treatment. The aim of this explorative study was to charac...

Objectives To develop a tool including exercise electrocardiography (ExECG) for patient-specific clinical likelihood estimation of patients with suspected obstructive coronary artery disease (CAD). Methods An ExECG-weighted clinical likelihood (ExECG-CL) model was developed in a training cohort of patients with suspected obstructive CAD undergoing...

Aims In chronic coronary syndrome (CCS) patients with documented coronary artery disease (CAD) ischemia detection by myocardial perfusion imaging (MPI) or an invasive approach are viable diagnostic strategies. We compared the diagnostic performance of quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT), positron em...

Patients with heart failure (HF) and reduced ejection fraction (HFrEF) are complex patients who often have a high prevalence of co-morbidities and risk factors. In the present study, we investigated the prognostic significance of left ventricular (LV) global longitudinal strain (GLS) along with important clinical and echocardiographic variables in...

Sedentary behavior (SB) and physical inactivity associate with impaired insulin sensitivity. We investigated whether an intervention aimed at a 1h reduction in daily SB during 6 months would improve insulin sensitivity in the weight-bearing thigh muscles. Forty-four sedentary inactive adults [mean age 58 (SD 7) years; 43% men] with metabolic syndro...

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Academy of Finland Turku University Hospital. Background Clinical risk scores for coronary artery disease (CAD) are used routinely in clinical practice to identify high risk patients in which diagnostic testing and therapy are warranted. Several recent...

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Academy of Finland, Turku University Hospital Background Coronary computed tomography angiography (CTA) and myocardial perfusion imaging (MPI) are powerful non-invasive tools to evaluate the patients with suspected coronary artery disease (CAD). Purpo...

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): State Research Funding for Turku University Hospital. Background Coronary computed tomography angiography (CCTA) is recommended for diagnostic workup of coronary artery disease (CAD) and is known to provide prognostic information. Howe...

Funding Acknowledgements Type of funding sources: None. Backgrounds Somatostatin receptor (SSTR) based positron emission tomography/computed tomography (PET/CT) is a novel approach for detecting myocardial inflammation and, consequently, cardiac sarcoidosis (CS). However, the diagnostic performance of SSTR PET/CT was only evaluated in small studie...

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): State Research Funding for Turku University Hospital. Background Combined anatomical and functional imaging enables detection of non-obstructive and obstructive coronary artery disease (CAD) as well as myocardial ischemia, and also pro...

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Academy of Finland Finnish foundation for cardiovascular research. Background Patients with prediabetes or diabetes are at increased risk of developing cardiovascular disease and cardiac events. First-line coronary computed tomography...

Nuclear imaging techniques can detect and quantify pathophysiological processes underlying heart failure, complementing evaluation of cardiac structure and function with other imaging modalities. Combined imaging of myocardial perfusion and metabolism can identify left ventricle dysfunction caused by myocardial ischemia that may be reversible after...

Background: Patients with prediabetes or diabetes are at increased risk of developing cardiovascular disease and adverse outcomes. First-line coronary computed tomography angiography (CTA) followed by selective use of positron emission tomography (PET) myocardial perfusion imaging is a feasible strategy to diagnose and risk-stratify patients with...

Risk stratification of patients with ischemic heart disease (IHD) still depends mainly on the left ventricular ejection fraction (LVEF). LV inward displacement (InD) is a novel parameter of LV systolic function, derived from feature tracking cardiac magnetic resonance (CMR) imaging. We aimed to investigate the prognostic impact of InD in patients w...

The coronary vascular volume to left ventricular mass (V/M) ratio assessed by coronary computed tomography angiography (CCTA) is a promising new parameter to investigate the relation of coronary vasculature to the myocardium supplied. It is hypothesized that hypertension decreases the ratio between coronary volume and myocardial mass by way of myoc...

Carimas is a multi-purpose medical imaging data processing tool, which can be used to visualize, analyze, and model different medical images in research. Originally, it was developed only for positron emission tomography data in 2009, but the use of this software has extended to many other tomography imaging modalities, such as computed tomography...

Aims: Combined anatomical and functional imaging enables detection of non-obstructive and obstructive coronary artery disease (CAD) as well as myocardial ischaemia. We evaluated sex differences in disease profile and outcomes after combined computed tomography angiography (CTA) and positron emission tomography (PET) perfusion imaging in patients w...

Introduction Poor cardiorespiratory fitness (CRF) is associated with adverse health outcomes. Previous observational and cross‐sectional studies have suggested that reducing sedentary behavior (SB) might improve CRF. Therefore, we investigated the effects of a 6‐month intervention of reducing SB on CRF in 64 sedentary inactive adults with metabolic...

Coronary computed tomographic angiography (CCTA) is becoming the first-line investigation for establishing the presence of coronary artery disease and, with fractional flow reserve (FFRCT), its haemodynamic significance. In patients without significant epicardial obstruction, its role is either to rule out atherosclerosis or to detect subclinical p...

Background: The various plaque components have been associated with ischemia and outcomes in patients with coronary artery disease (CAD). The main goal of this analysis was to test the hypothesis that, at patient level, the fraction of non-calcified plaque volume (PV) of total PV is associated with ischemia and outcomes in patients with CAD. This...

BACKGROUND Pericoronary adipose tissue (PCAT) attenuation has been associated with coronary inflammation and can be evaluated with coronary computed tomography angiography. The aims of this study were to compare the PCAT attenuation across precursors of culprit and nonculprit lesions of patients with acute coronary syndrome versus stable coronary a...

Angina pectoris and dyspnea in patients with normal or nonobstructive coronary vessels remains a diagnostic challenge. Invasive coronary angiography may identify up to 60% of patients with nonobstructive coronary artery disease (CAD), of whom nearly two-thirds may, in fact, have coronary microvascular dysfunction (CMD) that may account for their sy...

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....

Endothelial wall shear stress (ESS) is a biomechanical force which plays a role in the formation and evolution of atherosclerotic lesions. The purpose of this study is to evaluate coronary computed tomography angiography (CCTA)-based ESS in coronary arteries without atherosclerosis, and to assess factors affecting ESS values. CCTA images from patie...

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...

Several studies have shown an association between aortic stenosis (AS) and coronary atherosclerosis. This study aimed to evaluate the gender differences in aortic valve calcium (AVC) and coronary artery calcium (CAC) and the association between CAC and all-cause mortality in patients with severe AS. A total of 260 patients (80 ± 7 years, 39% men) w...

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...