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PET in Heart Failure - Methods and Applications
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
PET vid hjärtsvikt - metoder och tillämpningar (Swedish)
Abstract [en]

Positron Emission Tomography (PET) permits regional myocardial perfusion, fibrosis and oxidative metabolism to be non-invasively quantified with radioactive tracers such as [15O]-water and [1-11C]-acetate. PET is an established research tool in congestive heart failure (CHF), a major cause of morbidity and mortality. However, as CHF is a syndrome that eventually affects all aspects of cardiac and systemic hemodynamic function, more clinically relevant information from a single PET scan is desirable. The aim of this thesis therefore was to develop and implement some new concepts in cardiac PET.

A new method for the measurement of cardiac output with any tracer was validated in animal experiments and CHF patients. The early pulmonary retention of [1-11C]-acetate was inversely related to left ventricular (LV) function in animals and was directly proportional to lung water content and severity of LV diastolic dysfunction in patients.

Eight patients with acute myocardial infarction were followed with serial PET from 3 hours to 3 weeks after trombolytic treatment. PET revealed that myocardial perfusion and the extraction and utilization of fuel substrates all decreased closer to the infarct centre. The rate of oxygen utilization within the infarct at 3 h predicted degree of myocardial fibrosis, pulmonary oedema and tissue viability at 3 weeks.

Seventeen patients with CHF due to chronic ischemic cardiomyopathy and severely reduced LV function were evaluated with [1-11C]-acetate PET before and after coronary artery bypass surgery. There was a dramatic improvement in physical performance and symptoms, which was not correlated to the standard LV ejection indices. PET revealed that functional improvement was associated with improved LV loading conditions, reversed remodeling and homogenization of oxidative metabolism rather than increased output.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2004. , p. 53
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1387
Keywords [en]
Medicine, congestive heart failure, myocardial ischemia, positron emission tomography, left ventricular dysfunction, tracer kinetic models
Keywords [sv]
Medicin
National Category
Dermatology and Venereal Diseases
Identifiers
URN: urn:nbn:se:uu:diva-4654ISBN: 91-554-6085-2 (print)OAI: oai:DiVA.org:uu-4654DiVA, id: diva2:165396
Public defence
2004-12-09, Akademiska sjukhuset, Robergsalen, Ingång 40, 4tr, Akademiska Sjukhuset, Uppsala, 13:15
Opponent
Supervisors
Available from: 2004-11-15 Created: 2004-11-15Bibliographically approved
List of papers
1. Simple and accurate assessment of forward cardiac output by use of 1-[11C]acetate PET verified in a pig model
Open this publication in new window or tab >>Simple and accurate assessment of forward cardiac output by use of 1-[11C]acetate PET verified in a pig model
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2003 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 44, no 7, p. 1176-1183Article in journal (Refereed) Published
Abstract [en]

Dynamic 1-(11)C-acetate PET (AC-PET) allows quantification of myocardial blood flow and oxidative metabolism. We wanted to determine the accuracy of AC-PET in measuring cardiac output (CO) using first-pass analysis and the indicator dilution principle. Further, we wanted to investigate the pulmonary uptake of acetate in relation to left atrial filling pressures and ventricular function.

METHODS: Twenty-four steady-state experiments were performed in 5 domestic pigs. Pulmonary capillary wedge pressure (PCWP) and CO by thermodilution (CO(thermo)) were recorded invasively simultaneous with AC-PET scans at baseline (n = 9), dobutamine infusion (n = 6), high-dose metoprolol and morphine (n = 6), and angiotensinamide infusion (n = 3). 1-(11)C-Acetate was injected as a rapid manual bolus. Regions of interest (ROIs) were placed in the right (RV) and left (LV) heart cavities. Time-activity curves were constructed and the area under the curve (AUC) was integrated from beginning the scan to the time of visually determined recirculation by simple arithmetic. CO by PET (CO(PET)) was calculated as injected dose/AUC. Image handling and curve analysis were repeated by a blinded observer. Total pulmonary extravascular retention of (11)C, expressed as percentage of injected dose (lung-uptake %ID), was measured using a combination of transmission, (15)O-carbon monoxide, and AC-PET scans.

RESULTS: CO(thermo) ranged from 2.1 to 8.2 L/min. CO(PET) determined from both LV and RV was linearly related to CO(thermo) with slopes close to 1 (LV, r = 0.98; RV, r = 0.96; both P < 0.001). Interobserver reproducibility was r = 0.98, P < 0.001. The PCWP range was 6-14 mm Hg and the lung-uptake %ID was 2.7-8.5 %ID. When normalized to baseline, lung-uptake %ID was correlated with PCWP (r = 0.56, P = 0.01) and linearly correlated with LV input resistance (PCWP divided by CO(thermo); r = 0.91, P < 0.001). When both lung-uptake %ID and stroke volume were normalized to baseline, a piecewise linear relation was found (r = 0.95, P < 0.001).

CONCLUSION: Our results suggest that measurements of CO by AC-PET are feasible and accurate. Using RV ROIs might favor CO measurements by any injectable PET tracer. The lung-uptake %ID might be useful in evaluation of pulmonary congestion, but further studies are needed.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-92350 (URN)12843234 (PubMedID)
Available from: 2004-11-15 Created: 2004-11-15 Last updated: 2017-12-14Bibliographically approved
2. The central circulation in heart failure non-invasively evaluated with dynamic positron emission tomography
Open this publication in new window or tab >>The central circulation in heart failure non-invasively evaluated with dynamic positron emission tomography
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Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:uu:diva-92351 (URN)
Available from: 2004-11-15 Created: 2004-11-15Bibliographically approved
3. Development of myocardial microcirculation and metabolism in acute ST-elevation myocardial infarction evaluated with positron emission tomography
Open this publication in new window or tab >>Development of myocardial microcirculation and metabolism in acute ST-elevation myocardial infarction evaluated with positron emission tomography
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2005 (English)In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 12, no 1, p. 43-54Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Early reperfusion is an established therapeutic objective in acute myocardial infarction (MI). The relationship of regional myocardial microcirculation and metabolism toward outcome in acute human MI is not well known.

METHODS AND RESULTS: In 8 patients, positron emission tomography (PET) was performed with oxygen 15-labeled water at 3 hours, 24 hours, and 3 weeks after the start of fibrinolytic treatment, with carbon 11 acetate at 3 hours and with fluorine 18 fluorodeoxyglucose at 24 hours and 3 weeks. Absolute quantification of perfusion and water-perfusable tissue fraction (PTF), metabolic activity, and substrate extraction in 4 regions of interest was performed. Coronary angiography was performed at 24 hours. Short-term outcome at 3 weeks was evaluated by contractile reserve with dobutamine stress echocardiography and lung water measurements with PET. Early regional perfusion, PTF, and extraction and utilization of oxygen and glucose decreased closer to the infarct region ( P < .001 for all). Infarct-related oxygen utilization and extraction of oxygen and glucose were closely related to outcome ( P < .01 for all). PTF improved significantly in the infarct-related regions over time in proportion to early oxygen extraction and utilization.

CONCLUSIONS: This pilot study indicates that PET might be useful in the evaluation of treatment efficacy and that restoration of oxidative metabolism is more closely related to myocardial damage recovery than perfusion in the early phase after MI.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-92352 (URN)10.1016/j.nuclcard.2004.09.018 (DOI)15682365 (PubMedID)
Available from: 2004-11-15 Created: 2004-11-15 Last updated: 2017-12-14Bibliographically approved
4. Mechanisms of functional improvement after coronary artery bypass surgery in patients with prolonged ischemic cardiomyopathy and severe left ventricular dysfunction.
Open this publication in new window or tab >>Mechanisms of functional improvement after coronary artery bypass surgery in patients with prolonged ischemic cardiomyopathy and severe left ventricular dysfunction.
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Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-92353 (URN)
Available from: 2004-11-15 Created: 2004-11-15 Last updated: 2010-01-13Bibliographically approved

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