Philip Hasbak’s research while affiliated with Copenhagen University Hospital and other places

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Publications (138)


Pulmonary blood volume as a marker of adenosine‐induced cardiac hyperemia: A Rubidium‐82 study
  • Article
  • Full-text available

February 2025

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16 Reads

Clinical Physiology and Functional Imaging

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Jacob Peter Hartmann

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Philip Hasbak

Purpose To investigate the efficacy of pulmonary blood volume (PBV) as a marker of the cardiac hyperemic response to adenosine during myocardial perfusion imaging (MPI). Methods Forty healthy subjects underwent four consecutive Rubidium‐82 rest/adenosine‐stress MPI: two sessions were conducted without any caffeine consumption (baseline), while the remaining two sessions involved controlled caffeine consumption (arm 1: 100 and 300 mg; arm 2: 200 and 400 mg). We evaluate the ability of the stress‐to‐rest ratio of PBV (PBV ratio) to identify an adequate cardiac hyperemic response. The adequate hyperemic response was defined as a stress myocardial blood flow >2 mL/g/min and a corresponding myocardial flow reserve >68% of the maximum myocardial flow reserve obtained during the baseline scans. Results Based on 126 MPI sessions conducted in 40 subjects, the PBV ratio demonstrated a sensitivity of 78% and a specificity of 74% in detecting adequate cardiac hyperemia. The positive predictive value was 95%, while the negative predictive value was 36%. Conclusion The PBV ratio permits the identification of adequate hyperemic response with sensitivities and specificities comparable to existing markers.

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FIGURE 1. Visualization of myocardial segmentation and 15 3 15 3 15 mm volume of interest (green box) inserted in left ventricular lumen. Percentage uptake is relative to uptake within segmented left ventricle. HLA 5 horizontal long axis; VLA 5 vertical long axis.
FIGURE 2. Comparison of SNR and CNR in left ventricle and noise in blood pool (coefficient of variation) obtained for STD and STD 1 PRC images in 25 healthy volunteers. PRC improves SNR and CNR significantly in both rest and stress conditions. In contrast, noise in blood pool is preserved, suggesting that increased activity recovery in myocardial wall drives improvements in SNR and CNR. Numbers above each violin plot indicate median and interquartile range of measurements. CoV 5 coefficient of variation.
Positron Range Correction Helps Enhance the Image Quality of Cardiac 82 Rb PET/CT

February 2025

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22 Reads

Journal of Nuclear Medicine


Coronary Microvascular Dysfunction Years After Cessation of Anabolic Androgenic Steroid Use

December 2024

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14 Reads

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1 Citation

JAMA Network Open

IMPORTANCE Long-term use of anabolic androgenic steroids (AASs) is associated with a high risk of left ventricular hypertrophy, heart failure with reduced systolic function, and early sudden death, with the mechanism of progression being understudied. Early and persistent impaired myocardial microcirculation could be of clinical importance and a potential underlying mechanism of frequent and early cardiac disease among individuals with AAS use and a future potential target for intervention. OBJECTIVE To investigate coronary microcirculation by measuring myocardial flow reserve (MFR) in men with current and former AAS use compared with controls with no prior AAS use, using cardiac rubidium 82 (82Rb) positron emission tomography/computed tomography (PET/CT). DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study included men involved in recreational strength training without established cardiovascular disease grouped according to their history of AAS use. The study was conducted November 24, 2021, to August 16, 2023. EXPOSURE Cardiac PET/CT with 82Rb was performed at rest and after adenosine-induced stress. MAIN OUTCOME AND MEASURE The primary outcome of this study was the MFR among the study groups; a secondary outcome was the coronary calcium score. By definition, impaired myocardial microcirculation was determined using a cutoff of MFR less than 2, and subclinically impaired microcirculation was determined using a cutoff of MFR less than 2.5. RESULTS A total of 90 men (32 with current AAS use, 31 with former AAS use, and 27 controls) were included. Mean (SD) age was 35.1 (8.7) years. Elapsed duration since AAS cessation was a geometric mean of 1.5 (95% CI, 0.9-2.5) years. Eighteen men (58.1%) with former use discontinued AAS use more than 1 year before enrollment. Impaired MFR was present in those with current (6 [18.8%]) and former (1 [3.2%]) use, whereas no impairment was observed among the controls (P = .02). Subclinically impaired MFR was higher among men with current (9 [28.1%]) and former (8 [25.8%]) AAS use than the controls (1 [3.7%]) (P = .02). In a multivariable logistic regression model among men with former AAS use, every doubling of the accumulated weekly duration of AAS use (log2) was independently associated with a factor 2 increase in the risk of impaired MFR less than 2.5 (odds ratio, 2.1; 95% CI, 1.03-4.35; P = .04). CONCLUSIONS AND RELEVANCE In this study, men with former AAS use displayed impaired MFR years after AAS cessation, suggesting impaired coronary microcirculation persists beyond active use




Detection of infective endocarditis with [64Cu]Cu-DOTATATE positron emission tomography/computed tomography: a case series

August 2024

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9 Reads

European Heart Journal - Case Reports

Background Infective endocarditis (IE) is a serious and fatal condition, with prosthetic valve endocarditis representing the worst prognosis. The recommended nuclear imaging modality 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) has limitations. In this case series, we present two patients with IE scanned with a novel PET tracer [64Cu]Cu-DOTATATE ([64Cu]Cu-[1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetra acetic acid]-d-Phe1, Tyr3-octreotate). Case summary An 84-year-old female patient (Patient 1) with a biological mitral valve prosthesis (MVP) was admitted acutely from the outpatient clinic. Transoesophageal echocardiography showed vegetations on the MVP. The patient underwent [64Cu]Cu-DOTATATE PET/CT, which showed uptake at the site of infection. The patient underwent surgical valve replacement. The post-operative period was without significant complications, and the patient was discharged home. In another case, a 72-year-old male patient (Patient 2) with a medical history of mild mitral valve stenosis, aortic valve stenosis, and gastrointestinal stromal tumour was admitted to the hospital for back and abdominal pain and subfebrile episodes. Transoesophageal echocardiography showed large vegetations in the native aortic valve. The patient underwent [64Cu]Cu-DOTATATE PET/CT, which showed no uptake at the site of the suspected infection. The patient underwent surgical valve replacement. The post-operative period was characterized by Candida albicans sternitis, and after prolonged hospitalization, the patient died of respiratory failure as a complication of sepsis. Discussion In conclusion, this is the first case series presenting two patients with definite IE (modified Duke criteria), who were scanned with the novel [64Cu]Cu-DOTATATE PET/CT. Patient 1, with endocarditis in the MVP, showed an uptake of the tracer, while Patient 2, with native aortic valve endocarditis, did not show any uptake.


The association between pulmonary capillary wedge pressure (PCWP) at rest and myocardial flow reserve (MFR).
Coronary microvascular dysfunction and left heart filling pressures in patients with type 2 diabetes

July 2024

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26 Reads

Aims Patients with type 2 diabetes (T2D) have a high prevalence of diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF), which in turn leads to an increased risk of hospitalization and death. However, the factors of risk and their relative importance in leading to higher left ventricular filling pressures are still disputed. We sought to clarify the associations of a wide range of invasive and non‐invasive risk factors with cardiac filling pressures in high‐risk T2D patients. Methods and results Patients with T2D at high risk of cardiovascular events were prospectively enrolled in this study. Participants were thoroughly phenotyped including right heart catheterization at rest and during exercise, echocardiography, urinary excretion of albumin (UACR), and quantification of their myocardial blood flow rate (MFR) using cardiac ⁸²Rb‐PET/CT. Of the 37 patients included in the study, 22 (59%) patients met invasive criteria for HFpEF. Only 2 out of 39 variables emerged as independent factors associated with left ventricular filling pressure as assessed by pulmonary capillary wedge pressure (PCWP) at rest; history of hypertension (coefficient: 2.6 mmHg [0.3; 5.0], P = 0.030) and MFR (P = 0.026). We found a significant inverse association between MFR and PCWP with a coefficient of −2.3 mmHg (−4.3; −0.3) in PCWP per integer change of MFR. The MFR ranged from 1.18 to 3.68 in our study, which corresponds to a difference in PCWP of approximately 6 mmHg between patients with the lowest compared to the highest MFR. During exercise, only 2 variables emerged as borderline independent factors associated with PCWP: myocardial flow reserve (coefficient: −4.4 [−9.6; 0.8], P = 0.091) and beta‐blockers use (coefficient: 6.1 [−0.1; 12.4], P = 0.053). Conclusions In patients with type 2 diabetes without known HFpEF but risk factors for cardiovascular disease, myocardial blood flow rate was independently associated with PCWP at rest across the range from normal to abnormal left heart filling pressures. A clinically significant difference of 6 mmHg in PWCP was attributable to differences in MFR in patients with the lowest compared with the highest MFR values. This suggests that strategies than attenuate microvascular dysfunction could slow progression of increased left ventricular left heart filling pressures in patients at increased risk.


Figure 1. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) flow diagram of eligible patients for the current study. n, number of patients; 82 Rb-PET, rubidium positron emission tomography; COPD, chronic obstructive pulmonary disease; LAMA, longacting muscarinic antagonist; LABA, longacting b-2 agonist. Created with biorender.com.
Results from the linear mixed model that tested the effect of group (COPD/control), adenosine infusion, age, sex, corrected BSA, and the interaction between group and adenosine infusion on heart rate, SV, _ Q, MBTT, PBV, and MBF
Pulmonary blood volume measured by 82Rb-PET in patients with chronic obstructive pulmonary disease: a retrospective cohort study

April 2024

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35 Reads

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1 Citation

Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology

In patients with chronic obstructive pulmonary disease (COPD), pulmonary vascular dysfunction and destruction are observable before the onset of detectable emphysema, but it is unknown whether this is associated with central hypovolemia. We investigated if COPD patients have reduced pulmonary blood volume (PBV) evaluated by ⁸² Rb-positron emission tomography (PET) at rest and during adenosine-induced hyperemia. This single-center retrospective cohort study assessed 6301 ⁸² Rb-PET myocardial perfusion imaging (MPI) examinations performed over a 6-year period. We compared 77 COPD patients with 44 healthy kidney donors (controls). Cardiac output (Q̇) and mean ⁸² Rb bolus transit time (MBTT) were used to calculate PBV. Q̇ was similar at rest (COPD: 3649 ± 120 mL vs. control: 3891 ± 160 mL, p=0.368) but lower in COPD patients compared to controls during adenosine infusion (COPD: 5432 ± 124 mL vs. control: 6185 ± 161 mL, p < 0.050). MBTT was shorter in COPD patients compared to controls at rest (COPD: 8.7 ± 0.28 seconds vs. control: 11.4 ± 0.37 seconds, p < 0.001) and during adenosine infusion (COPD: 9.2 ± 0.28 seconds vs. control: 10.2 ± 0.37 seconds, p < 0.014). PBV was lower in COPD patients, even after adjustment for body surface area, sex, and age at rest (COPD: 530 (29) mL vs. 708 (38) mL, p < 0.001) and during adenosine infusion (COPD: 826 (29) mL vs. 1044 (38) mL, p<0.001). In conclusion, patients with COPD show evidence of central hypovolemia, but it remains to be determined whether this has any diagnostic or prognostic impact.


Type I interferon induced differences in exercise adaptations of aerobic capacity and fatigue in systemic lupus erythematosus -Protocol for a randomised controlled single-centre trial Correspondence

February 2024

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78 Reads

Type I interferon induced differences in exercise adaptations of aerobic capacity and fatigue in systemic lupus erythematosus-Protocol for a randomised controlled single-centre trial Protocol for a HIIT exercise trial illuminating exercise as intervention for aerobic capacity and fatigue, differentiating SLE patients on their type 1 IFN-signature.


Increased Subclinical Coronary Artery Pathology in Type 2 Diabetes With Albuminuria

November 2023

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23 Reads

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2 Citations

Diabetes

Diabetes affects the kidneys, and the presence of albuminuria reflects widespread vascular damage and is a risk factor for cardiovascular disease (CVD). Still, the pathophysiological association between albuminuria and CVD remains incompletely understood. Recent advances in noninvasive imaging enable functional assessment of coronary artery pathology and present an opportunity to explore the association between albuminuria and CVD. In this cross-sectional study, we evaluated the presence of subclinical coronary artery pathology in people with type 2 diabetes, free of overt CVD. Using multimodal imaging, we assessed the coronary microcalcification activity (18F-sodium fluoride positron emission tomography/computed tomography [PET/CT], plaque inflammation [64Cu-DOTATATE PET/CT], and myocardial flow reserve [82Rb PET/CT]). The study population consisted of 90 participants, stratified by albuminuria; 60 had historic or current albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g]), and 30 had normoalbuminuria (UACR <30 mg/g). We demonstrated that any albuminuria (historic or current) was associated with a more severe phenotype, in particular, higher levels of microcalcifications and impaired myocardial microvascular function; however, coronary inflammation activity was similar in people with and without albuminuria. Our findings establish a potential underlying mechanism connecting cardiovascular and kidney diseases and could indicate the initial stages of the cardiorenal syndrome. Article Highlights


Citations (69)


... Another promising PET tracer for use in people with diabetes is 18 F-sodium fluoride ( 18 F-NaF), which targets microcalcifications within atherosclerotic plaques, indicating active calcification processes and plaque instability. NaF-PET's sensitivity for microcalcification may allow for the assessment of early, subclinical atherosclerosis, a diagnosis with special importance in people with diabetes [43]. ...

Reference:

Advances in Imaging Techniques for Assessing Myocardial Microcirculation in People with Diabetes: An Overview of Current Techniques, Emerging Techniques, and Clinical Applications
Increased Subclinical Coronary Artery Pathology in Type 2 Diabetes With Albuminuria
  • Citing Article
  • November 2023

Diabetes

... Naturally, several factors, such as shifts in the heart during the PET emission acquisition (myocardial motion, breathing, and myocardial creep), may further affect PRC performance. Recent research from our center has identified that myocardial creep and cardiorespiratory motion affect AUC assessments, particularly in patient cohorts similar to those in this study (19). The motioninduced shift in the left ventricular wall (and concomitant nonlinear changes in tissue distributions) will reduce the activity recovery of PRC after processing. ...

Myocardial creep and cardiorespiratory motion correction improves diagnostic accuracy of Rubidium-82 cardiac positron emission tomography

Journal of Nuclear Cardiology

... For example, Heerspink et al. 18 observed a decrease in mGFR of 8% relative to placebo following dapagliflozin 10 mg/day for 12 weeks in people with T2D. Similarly, Jurgens et al. 19 observed a decrease in mGFR of 8 mL/min relative to placebo following empagliflozin 25 mg/day for 13 weeks in people with T2D, and Jensen et al. 20 observed a decrease of 7.5 mL/min relative to placebo following empagliflozin 10 mg/day for 12 weeks in people with heart failure. Despite the decrease in mGFR, we did not observe a corresponding change in any filtration markers or eGFR according to any equation. ...

The effects of empagliflozin on measured glomerular filtration rate and estimated extracellular and plasma volumes in patients with type 2 diabetes
  • Citing Article
  • July 2023

Diabetes Obesity and Metabolism

... This study aims to test the feasibility of using cardiac 82 Rb-PET to estimate the pulmonary blood volume (PBV) as a marker for a sufficient hyperemic response (Lassen et al., 2023). The PBV depends on cardiac and pulmonary function, which the baroreceptor system monitors. ...

Pulmonary blood volume assessment from a standard cardiac rubidium-82 imaging protocol: impact of adenosine-induced hyperemia

Journal of Nuclear Cardiology

... In this paper, we seek to further improve clinical PET image quality by correcting for both respiratory motion during the PET scan and potential mismatch between CT and PET DDG using a novel AIR-PETCT algorithm. The blind assessment of the validation cohort demonstrated that the AIR-PETCT algorithm is robust, consistently maintaining or improving subjective image quality and semiquantitative development and with research groups approaching the problem from different strategies: from the before mentioned breath-hold techniques [22], device-based [23] or DDG [11,14,24,25] to more recent methods to align PET images and PET/CT images such as the FALCON tool that uses diffeomorphic motion compensation scheme using both affine alignments and nonrigid deformations to align dynamic WB PET series [26], and deep-learning approaches to generate synthetic CTs based on non-attenuation corrected PET emission data [25,26] removing potential misalignment between the CT and the PET. ...

Fully Automated, Fast Motion Correction of Dynamic Whole-Body and Total-Body PET/CT Imaging Studies
  • Citing Article
  • June 2023

Journal of Nuclear Medicine

... A study by Bulut et al. (2023) showed that people who have used AASs in the past might have problems with the small blood vessels in their heart. The study compared people who currently or formerly used AAS to those who did not and found that the former group had a decrease in the heart muscle blood flow reserve, as measured by a type of imaging test-positron emission tomogrpahy-computerized tomography using Rubidium Rb-82 injection (PET/CT Rb-82). ...

Previous use of anabolic androgenic steroids is associated with persistent impaired myocardial microcirulation
  • Citing Article
  • May 2023

Endocrine Abstracts

... For example, Wu et al. reported only trends toward lower perfusion defects and metabolism deficits in vascular endothelial growth factor-treated animal models, without statistically significant changes (25). Nevertheless, as here, several studies suggested that elevated a v b 3 integrin expression after ischemic myocardial injury is associated with subsequent improvement in regional left ventricular function (6,11,12,26,27). Recently, using the same PET tracer with 68 Ga-NODAGA-RGD, Nammas et al. reported in humans that a v b 3 integrin expression levels 1 wk after MI were linked to regional and global systolic dysfunction, as well as elevated left ventricular filling pressure, and predicted improved global left ventricular function 6 mo after MI (12). ...

[68Ga]Ga-NODAGA-E[(cRGDyK)]2 angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure

Journal of Nuclear Cardiology

... CT is widely used in the evaluation of multiple cardiovascular conditions, although the focus has been mainly on the assessment of coronary blood flow and coronary microcirculation, [102][103][104][105][106] with relatively few studies using CT imaging to assess the peripheral microcirculation [107][108][109]. Our group applied CT angiography successfully in the measurement of physiologic changes in epicardial vessel diameter in response to dobutamine and adenosine vasoactive responses, and the secondary flow-mediated response associated with microvascular vasodilation [110]. ...

Quantification of myocardial blood flow using dynamic myocardial CT perfusion compared with 82Rb PET
  • Citing Article
  • April 2023

Journal of Cardiovascular Computed Tomography

... There are new development directions for larger-area wearable devices as current form factors do not meet use-case demands. Some examples include the use of single-lead wearable devices in comparison to the goldstandard 12-lead systems for electrocardiography (ECG) [11]. The current limitation in the application of larger wearable patches is that there is a minimal understanding of skin wearable devices regarding user perception, compliance, comfort, and wearability. ...

Wireless Single-Lead versus Standard 12-Lead ECG, for ST-Segment Deviation during Adenosine Cardiac Stress Scintigraphy

... 1 Human studies have suggested that SGLT2 inhibitors reduce blood glucose, decrease body weight, improve cardiac function, and reduce plasma volume. 1 Mechanistic substudies of randomized controlled trials have suggested that the efficacy of SGLT2 inhibitors in preventing cardiovascular events is unlikely to be explained by improvement in blood glucose control alone ( Table 1). [3][4][5][6][7][8][9] Similarly, SGLT2 inhibitors have been reported to not reduce systemic markers of inflammation, such as C-reactive protein, 4 and have no effect on circulating concentrations of insulin-like growth factor-1, 3 or myocardial energy metabolism as assessed by phosphorus magnetic resonance spectroscopy and dobutamine stress echo. 7 Smaller randomized trials have suggested that some SGLT2 inhibitors, such as enavogliflozin, reduce blood pressure, low-density lipoprotein-cholesterol (LDL-C), and triglyceride, 8 although the degree of effect appears too small and the finding too inconsistent to explain the cardiovascular benefits of SGLT2 inhibitors reported. ...

Reduction of cardiac adipose tissue volume with short‐term empagliflozin treatment in patients with type 2 diabetes: A substudy from the SIMPLE randomized clinical trial

Diabetes Obesity and Metabolism