| 1. |
- Grönman, Maria, et al.
(författare)
-
Assessment of myocardial viability with [15O]water PET : A validation study in experimental myocardial infarction
- 2021
-
Ingår i: Journal of Nuclear Cardiology. - : Springer Nature. - 1071-3581 .- 1532-6551. ; 28:4, s. 1271-1280
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Assessment of myocardial viability is often needed in patients with chest pain and reduced ejection fraction. We evaluated the performance of reduced resting MBF, perfusable tissue fraction (PTF), and perfusable tissue index (PTI) in the assessment of myocardial viability in a pig model of myocardial infarction (MI).METHODS AND RESULTS: Pigs underwent resting [15O]water PET perfusion study 12 weeks after surgical (n = 16) or 2 weeks after catheter-based (n = 4) occlusion of the proximal left anterior descending coronary artery. MBF, PTF, and PTI were compared with volume fraction of MI in matched segments as assessed by triphenyl tetrazolium chloride staining of LV slices. MBF and PTF were lower in infarcted than non-infarcted segments. Segmental analysis of MBF showed similar area under the curve (AUC) of 0.85, 0.86, and 0.90 with relative MBF, PTF, and PTI for the detection of viable myocardium defined as infarct volume fraction of < 75%. Cut-off values of relative MBF of ≥ 67% and PTF of ≥ 66% resulted in accuracies of 90% and 81%, respectively.CONCLUSIONS: Our results indicate that resting MBF, PTF, and PTI based on [15O]water PET perfusion imaging are useful for the assessment of myocardial viability.
|
|
| 2. |
- Rissanen, Tuomas T., et al.
(författare)
-
The bottleneck stent model for chronic myocardial ischemia and heart failure in pigs
- 2013
-
Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 305:9, s. H1297-H1308
-
Tidskriftsartikel (refereegranskat)abstract
- A large animal model of chronic myocardial ischemia and heart failure is crucial for the development of novel therapeutic approaches. In this study we developed a novel percutaneous one-and two-vessel model for chronic myocardial ischemia using a stent coated with a polytetrafluoroethylene tube formed in a bottleneck shape. The bottleneck stent was implanted in the proximal left anterior descending (LAD) or proximal circumflex artery (LCX), or in both proximal LCX and mid LAD 1 wk later (2-vessel model), and pigs were followed for 4-5 wk. Ejection fraction (EF), infarct size, collateral growth, and myocardial perfusion were assessed. Pigs were given antiarrhythmic medication to prevent sudden death. The occlusion time of the bottleneck stent and the timing of myocardial infarction could be modulated by the duration of antiplatelet medication. Fractional flow reserve measurements and positron emission tomography imaging showed severe ischemia after bottleneck stenting covering over 50% of the left ventricle in the proximal LAD model. Complete coronary occlusion was necessary for significant collateral growth, which mostly had occurred already during the first wk after the stent occlusion. Dynamic and competitive collateral growth patterns were observed. EF declined from 64 to 41% in the LCX model and to 44% in the LAD model 4 wk after stenting with 12 and 21% infarcted left ventricle in the LCX and LAD models, respectively. The mortality was 32 and 37% in the LCX and LAD models but very (71%) high in the two-vessel disease model. The implantation of a novel bottleneck stent in the proximal LAD or LCX is a novel porcine model of reversible myocardial ischemia (open stent) and ischemic heart failure (occluded stent) and is feasible for the development of new therapeutic approaches.
|
|
| 3. |
- Besson, Florent L, et al.
(författare)
-
A systematic review for the evidence of recommendations and guidelines in hybrid nuclear cardiovascular imaging.
- 2024
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - 1619-7070 .- 1619-7089.
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study aimed to evaluate the level of evidence of expert recommendations and guidelines for clinical indications and procedurals in hybrid nuclear cardiovascular imaging.METHODS: From inception to August 2023, a PubMed literature analysis of the latest version of guidelines for clinical hybrid cardiovascular imaging techniques including SPECT(/CT), PET(/CT), and PET(/MRI) was performed in two categories: (1) for clinical indications for all-in primary diagnosis; subgroup in prognosis and therapy evaluation; and for (2) imaging procedurals. We surveyed to what degree these followed a standard methodology to collect the data and provide levels of evidence, and for which topic systematic review evidence was executed.RESULTS: A total of 76 guidelines, published between 2013 and 2023, were included. The evidence of guidelines was based on systematic reviews in 7.9% of cases, non-systematic reviews in 47.4% of cases, a mix of systematic and non-systematic reviews in 19.7%, and 25% of guidelines did not report any evidence. Search strategy was reported in 36.8% of cases. Strengths of recommendation were clearly reported in 25% of guidelines. The notion of external review was explicitly reported in 23.7% of cases. Finally, the support of a methodologist was reported in 11.8% of the included guidelines.CONCLUSION: The use of evidence procedures for developing for evidence-based cardiovascular hybrid imaging recommendations and guidelines is currently suboptimal, highlighting the need for more standardized methodological procedures.
|
|
| 4. |
- Danad, Ibrahim, et al.
(författare)
-
Quantitative Assessment of Myocardial Perfusion in the Detection of Significant Coronary Artery Disease Cutoff Values and Diagnostic Accuracy of Quantitative [O-15]H2O PET Imaging
- 2014
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 64:14, s. 1464-1475
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Recent studies have demonstrated improved diagnostic accuracy for detecting coronary artery disease (CAD) when myocardial blood flow (MBF) is quantified in absolute terms, but there are no uniformly accepted cutoff values for hemodynamically significant CAD. OBJECTIVES The goal of this study was to determine cutoff values for absolute MBF and to evaluate the diagnostic accuracy of quantitative [O-15]H2O positron emission tomography (PET). METHODS A total of 330 patients underwent both quantitative [O-15]H2O PET imaging and invasive coronary angiography in conjunction with fractional flow reserve measurements. A stenosis >90% and/or fractional flow reserve <= 0.80 was considered obstructive; a stenosis <30% and/or fractional flow reserve >0.80 was nonobstructive. RESULTS Hemodynamically significant CAD was diagnosed in 116 (41%) of 281 patients who fulfilled study criteria for CAD. Resting perfusion was 1.00 +/- 0.25 and 0.92 +/- 0.23 ml/min/g in regions supplied by nonstenotic and significantly stenosed vessels, respectively (p < 0.001). During stress, perfusion increased to 3.26 +/- 1.04 ml/min/g and 1.73 +/- 0.67 ml/min/g, respectively (p < 0.001). The optimal cutoff values were 2.3 and 2.5 for hyperemic MBF and myocardial flow reserve, respectively. For MBF, these cutoff values showed a sensitivity, specificity, and accuracy for detecting significant CAD of 89%, 84%, and 86%, respectively, at a per-patient level and 87%, 85%, and 85% at a per-vessel level. The corresponding myocardial flow reserve values were 86%, 72%, and 78% (per patient) and 80%, 82%, and 81% (per vessel). Age and sex significantly affected diagnostic accuracy of quantitative PET. CONCLUSIONS Quantitative MBF measurements with the use of [O-15]H2O PET provided high diagnostic performance, but both sex and age should be taken into account.
|
|
| 5. |
- Kero, Tanja, et al.
(författare)
-
Quantitative myocardial perfusion response to adenosine and regadenoson in patients with suspected coronary artery disease
- 2022
-
Ingår i: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 29:1, s. 24-36
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of the present study was to compare the quantitative flow responses of regadenoson against adenosine using cardiac 15O-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 analysis in 21 patients who underwent rest and adenosine 15O-water PET scans followed by rest and regadenoson 15O-water PET scans.RESULTS: Global mean (± SD) MBF values at rest and stress were 0.92 ± 0.27 and 2.68 ± 0.80 mL·g·min for the adenosine study and 0.95 ± 0.29 and 2.76 ± 0.79 mL·g·min for the regadenoson study (P = 0.55 and P = 0.49). The correlations between global and regional adenosine- and regadenoson-based stress MBF were strong (r = 0.80 and r = 0.77). The biases were small for both global and regional MBF comparisons (0.08 and 0.09 mL·min·g), but the limits of agreement were wide for stress MBF.CONCLUSION: The correlation between regadenoson- and adenosine-induced hyperemic MBF was strong but the agreement was only moderate indicating that established cut-off values for 150-water PET should be used cautiously if using regadenoson as vasodilator.
|
|
| 6. |
- Michaëlsson, Erik, et al.
(författare)
-
Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF.
- 2023
-
Ingår i: JACC. Heart failure. - 2213-1787. ; 11:7, s. 775-87
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic microvascular dysfunction and inflammation are postulated to play a pathophysiologic role in heart failure with preserved ejection fraction (HFpEF).This study aimed to identify biomarker profiles associated with clinical outcomes in HFpEF and investigate how inhibition of the neutrophil-derived reactive oxygen species-producing enzyme, myeloperoxidase, affects these biomarkers.Using supervised principal component analyses, the investigators assessed the associations between baseline plasma proteomic Olink biomarkers and clinical outcomes in 3 independent observational HFpEF cohorts (n=86, n=216, and n=242). These profiles were then compared with the biomarker profiles discriminating patients treated with active drug vs placebo in SATELLITE (Safety and Tolerability Study of AZD4831 in Patients With HeartFailure), a double-blind randomized 3-month trial evaluating safety and tolerability of the myeloperoxidase inhibitor AZD4831 in HFpEF (n=41). Pathophysiological pathways were inferred from the biomarker profiles by interrogation of the Ingenuity Knowledge database.TNF-R1, TRAIL-R2, GDF15, U-PAR, and ADM were the top individual biomarkers associated with heart failure hospitalization or death, and FABP4, HGF, RARRES2, CSTB, and FGF23 were associated with lower functional capacity and poorer quality of life. AZD4831 downregulated many markers (most significantly CDCP1, PRELP, CX3CL1, LIFR, VSIG2). There was remarkable consistency among pathways associated with clinical outcomes in the observational HFpEF cohorts, the top canonical pathways being associated with tumor microenvironments, wound healing signaling, and cardiac hypertrophy signaling. These pathways were predicted to be downregulated in AZD4831 relative to placebo-treated patients.Biomarker pathways that were most strongly associated with clinical outcomes were also the ones reduced by AZD4831. These results support the further investigation of myeloperoxidase inhibition in HFpEF.
|
|
| 7. |
- Myhre, Peder L., et al.
(författare)
-
External validation of a deep learning algorithm for automated echocardiographic strain measurements
- 2024
-
Ingår i: EUROPEAN HEART JOURNAL - DIGITAL HEALTH. - 2634-3916. ; 5:1, s. 60-68
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Echocardiographic strain imaging reflects myocardial deformation and is a sensitive measure of cardiac function and wall-motion abnormalities. Deep learning (DL) algorithms could automate the interpretation of echocardiographic strain imaging.Methods and results We developed and trained an automated DL-based algorithm for left ventricular (LV) strain measurements in an internal dataset. Global longitudinal strain (GLS) was validated externally in (i) a real-world Taiwanese cohort of participants with and without heart failure (HF), (ii) a core-lab measured dataset from the multinational prevalence of microvascular dysfunction-HF and preserved ejection fraction (PROMIS-HFpEF) study, and regional strain in (iii) the HMC-QU-MI study of patients with suspected myocardial infarction. Outcomes included measures of agreement [bias, mean absolute difference (MAD), root-mean-squared-error (RMSE), and Pearson's correlation (R)] and area under the curve (AUC) to identify HF and regional wall-motion abnormalities. The DL workflow successfully analysed 3741 (89%) studies in the Taiwanese cohort, 176 (96%) in PROMIS-HFpEF, and 158 (98%) in HMC-QU-MI. Automated GLS showed good agreement with manual measurements (mean +/- SD): -18.9 +/- 4.5% vs. -18.2 +/- 4.4%, respectively, bias 0.68 +/- 2.52%, MAD 2.0 +/- 1.67, RMSE = 2.61, R = 0.84 in the Taiwanese cohort; and -15.4 +/- 4.1% vs. -15.9 +/- 3.6%, respectively, bias -0.65 +/- 2.71%, MAD 2.19 +/- 1.71, RMSE = 2.78, R = 0.76 in PROMIS-HFpEF. In the Taiwanese cohort, automated GLS accurately identified patients with HF (AUC = 0.89 for total HF and AUC = 0.98 for HF with reduced ejection fraction). In HMC-QU-MI, automated regional strain identified regional wall-motion abnormalities with an average AUC = 0.80.Conclusion DL algorithms can interpret echocardiographic strain images with similar accuracy as conventional measurements. These results highlight the potential of DL algorithms to democratize the use of cardiac strain measurements and reduce time-spent and costs for echo labs globally. Graphical Abstract
|
|
| 8. |
- Pesonen, Erkki, et al.
(författare)
-
Infections and endothelial cell apoptosis
- 2010
-
Ingår i: Cardiology in the Young. - 1467-1107. ; 20:Suppl 1, s. 224-224
-
Konferensbidrag (refereegranskat)abstract
- Objectives: Endothelial cells of coronary arteries undergo apoptosis in patients with coronary artery disease. Carotid artery ultrasound studies show that after acute infections intima media thickness is increased. The possible effects of infections on endothelial cell apoptosis and the presence of apoptosis in early life remain unknown. Methods: Chlamydia pneumonia was inoculated three times at three weeks intervals to half of 32 piglets starting at the age of 8 weeks. Half of the piglets received cholesterol feeding. Morphological studies were done at the age of 19 weeks. Right coronary arteries were carefully excised and trimmed for excess tissue. The vessels were cut perpendicular to the long axis and sectioned at 5-μm thickness. TUNEL-assay was based on nick end labelling and staining of internucleosomal DNA fragments that are the biochemical hallmark of apoptosis. The percentage of apoptotic endothelial cells from intact endothe-lial cells was calculated using light microscopy. Results. Endothelial apoptosis appeared in 0.13% (SD 0.30%) of endothelial cells of non-infected piglets but in 0.75% (SD 0.62) of infected piglets (p <0.005, t-test). In piglets fed with normal diet apoptosis appeared in 1.1% but in those on cholesterol rich diet the prevalence of apoptosis was lower 0.43% (SD 0.42). Conclusions: Infections amplify endothelial cell apoptosis. The finding supports the notion that infection has a pro-atherogenic effect particularly in early life. Hypercholesterolemic diet did not further stimulate apoptosis.
|
|
| 9. |
- Prescott, Eva, et al.
(författare)
-
Design and rationale of FLAVOUR : A phase IIa efficacy study of the 5-lipoxygenase activating protein antagonist AZD5718 in patients with recent myocardial infarction
- 2020
-
Ingår i: Contemporary Clinical Trials Communications. - : Elsevier BV. - 2451-8654. ; 19
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with coronary artery disease remain at increased risk of recurrent life-threatening cardiovascular events even after adequate guideline-based treatment of conventional risk factors, including blood lipid levels. Inflammation is a critical pathway in the pathogenesis of atherosclerosis and is independently associated with risk of recurrent cardiovascular events. Leukotrienes are potent pro-inflammatory and vasoactive mediators synthesized by leukocytes in atherosclerotic lesions. AZD5718 is a novel antagonist of 5-lipoxygenase activating protein that suppresses leukotriene biosynthesis. FLAVOUR is a phase IIa efficacy and safety study of AZD5718 in patients with myocardial infarction 1–4 weeks before randomization. Stenosis of the left anterior descending coronary artery after percutaneous intervention must be <50%, and Thrombolysis In Myocardial Infarction flow grade must be ≥ 2. Enrolled participants receive standard care plus oral AZD5718 200 mg, 50 mg, or placebo once daily for up to 12 weeks (extended from 4 weeks by protocol amendment). The planned sample size is 100 participants randomized to 12 weeks’ treatment. Change in urine leukotriene E4 levels is the primary efficacy outcome. FLAVOUR also aims to evaluate whether AZD5718 can improve coronary microvascular function, as measured by transthoracic colour Doppler-assisted coronary flow velocity reserve. Centrally pretrained study sonographers use standardized protocols and equipment. Additional outcomes include assessment of comprehensive echocardiographic parameters (including coronary flow, global strain, early diastolic strain rate and left ventricular ejection fraction), arterial stiffness, biomarkers, health-related quality of life, and safety. Specific anti-inflammatory therapies may represent novel promising treatments to reduce residual risk in patients with coronary artery disease. By combining primary pharmacodynamic and secondary cardiovascular surrogate efficacy outcomes, FLAVOUR aims to investigate the mechanistic basis and potential benefits of AZD5718 treatment in patients with coronary artery disease.
|
|
| 10. |
- Prescott, Eva, et al.
(författare)
-
Safety and efficacy of the 5-lipoxygenase-activating protein inhibitor AZD5718 in patients with recent myocardial infarction: The phase 2a FLAVOUR study.
- 2022
-
Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 365, s. 34-40
-
Tidskriftsartikel (refereegranskat)abstract
- Leukotrienes are pro-inflammatory vasoactive lipid mediators implicated in the pathophysiology of atherosclerotic cardiovascular disease. We studied the effect of the 5-lipoxygenase-activating protein inhibitor AZD5718 on leukotriene biosynthesis and coronary microvascular function in a single-blind, phase 2a study.Patients 7-28days after myocardial infarction (±ST elevation), with <50% left anterior descending coronary artery stenosis and Thrombolysis in Myocardial Infarction flow grade≥2 after percutaneous coronary intervention, were randomized 2:1:2 to once-daily AZD5718 200mg or 50mg, or placebo, in 4- and 12-week cohorts. Change in urine leukotriene E4 (uLTE4) was the primary endpoint, and coronary flow velocity reserve (CFVR; via echocardiography) was the key secondary endpoint.Of 129 randomized patients, 128 received treatment (200mg, n=52; 50mg, n=25; placebo, n=51). Statistically significant reductions in uLTE4 levels of >80% were observed in both AZD5718 groups versus the placebo group at 4 and 12weeks. No significant changes in CFVR were observed for AZD5718 versus placebo. Adverse events (AEs) occurred in 12/18, 3/6 and 6/13 patients receiving 200mg, 50mg and placebo, respectively, in the 4-week cohort, and in 27/34, 14/19 and 24/38 patients, respectively, in the 12-week cohort. Serious AEs in seven patients receiving AZD5718 and four receiving placebo were not treatment-related, and there were no deaths.In patients with recent myocardial infarction, AZD5718 was well tolerated, and leukotriene biosynthesis was dose-dependently inhibited. No significant changes in CFVR were detected.gov identifier: NCT03317002.
|
|
