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Cardiac PET is increasingly performed with dynamic imaging to measure tracer pharmacokinetics in the myocardium. If the early time frames of the PET protocol are sufficiently short and the total amount of injected radioactivity is correctly measured the indicator dilution principle can be applied to PET with most tracers in clinical use, similar to invasive and other noninvasive techniques. The first-pass of the tracer through the heart and lungs can be used to quantify some highly important aspects of cardiovascular function, such as forward cardiac output, transit times, and partial volumes in the central compartments. Additionally, ECG-gated first pass images provide direct access to cardiac volumes and ejection fractions, even for tracers with poor trapping in the myocardial wall, for instance 15O-water. This review summarizes the basic approaches of the indicator dilution principle in clinical use with invasive techniques, and how these techniques can be integrated into a cardiac PET scan., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background This study evaluated myocardial oxygen consumption (MVO 2 ) and myocardial external efficiency (MEE) in patients with cardiac amyloidosis (CA). Furthermore, we compared MEE and MVO 2 in subjects with light chain amyloidosis versus transthyretin (ATTR) amyloidosis. Methods and Results The study population comprised 40 subjects: 25 patients with confirmed CA and 15 control subjects. All subjects underwent an 11 C-acetate positron emission tomography. Furthermore, the CA patients underwent comprehensive echocardiography and right heart catheterization during a symptom-limited, semi-supine exercise test. MEE was calculated from 11 C-acetate positron emission tomography as the ratio of left ventricular (LV) stroke work and the energy equivalent of MVO 2 . Myocardial work efficiency was calculated as echocardiography-derived work pressure product divided by three-dimensional LV mass. CA patients had significantly lower LV-ejection fraction (54±13% versus 63±4%, P<0.05) and LV-global longitudinal strain (LVGLS) (12±4% versus 19±2%, P<0.0001) and a more restrictive filling pattern (E/e'-ratio 18 [12-25] versus 8 [7-9], P<0.0001) than controls. MEE was severely reduced (13±5% versus 22±5%, P<0.0001) whereas total MVO 2 was higher (18±6 mL/min versus 13±3 mL/min, P<0.01) in CA patients than controls. MEE decreased with increasing New York Heart Association symptom burden ( P<0.0001). We found a good relationship between MEE and peak exercise systolic performance (LVGLS: R 2 =0.60, P<0.0001; myocardial work efficiency: R 2 =0.48, P<0.0001; cardiac index: R 2 =0.52, P<0.0001) and between MEE and myocardial blood flow ( R 2 =0.44, P<0.0001). Conclusion Myocardial oxidative metabolism is disturbed in CA patients with increased total MVO 2 and reduced MEE. MEE correlated significantly with echocardiographic derived systolic parameters such as myocardial work efficiency and LVGLS that might be used as surrogate MEE markers.

Background: Reduced myocardial efficiency represents a target for therapy in hypertrophic cardiomyopathy although therapeutic benefit may depend on disease stage. Here, we determined disease stage-dependent changes in myocardial efficiency and effects of myectomy surgery., Methods and Results: Myocardial external efficiency (MEE) was determined in 27 asymptomatic mutation carriers (genotype positive/phenotype negative), 10 patients with hypertrophic obstructive cardiomyopathy (HOCM), 10 patients with aortic valve stenosis, and 14 healthy individuals using [ 11 C]-acetate positron emission tomography and cardiovascular magnetic resonance imaging. Follow-up measurements were performed in HOCM and aortic valve stenosis patients 4 months after surgery. External work did not differ in HOCM compared with controls, whereas myocardial oxygen consumption was lower in HOCM. Because of a higher cardiac mass, total cardiac oxygen consumption was significantly higher in HOCM than in controls and genotype positive/phenotype negative. MEE was significantly lower in genotype positive/phenotype negative than in controls (28±6% versus 42±6%) and was further decreased in HOCM (22±5%). In contrast to patients with aortic valve stenosis, MEE was not improved in patients with HOCM after surgery, which was explained by opposite changes in the septum (decrease) and lateral (increase) wall., Conclusions: Different mechanisms underlie reduced MEE at the early and advanced stage of hypertrophic cardiomyopathy. The initial increase and subsequent reduction in myocardial oxygen consumption during disease progression indicates that energy deficiency is a primary mutation-related event, whereas mechanisms secondary to disease remodeling underlie low MEE in HOCM. Our data highlight that the benefit of therapies to improve energetic status of the heart may vary depending on the disease stage and that treatment should be initiated before cardiac remodeling., (© 2017 American Heart Association, Inc.)

Background: Mismatch between myocardial innervation and perfusion assessed with positron emission tomography (PET) is a potential risk marker for ventricular arrhythmias in patients with ischemic cardiomyopathy. This mismatch zone originates from residual viable myocardium that has sustained ischemic nerve injury. Heterogenic scar size assessed with late gadolinium-enhanced (LGE) cardiac magnetic resonance imaging (CMR) is also a risk marker of ventricular arrhythmias. These two imaging parameters may represent identical morphological tissue features. The current study explored the relation between innervation-perfusion mismatch and heterogenic scar size., Methods: Twenty-eight patients (26 males, age 67 ± 8 years) with ischemic cardiomyopathy and a left ventricular ejection fraction below 35%, eligible for ICD implantation were included. All patients underwent both [ 11 C]-hydroxyephedrine and [ 15 O]-water PET studies to assess myocardial sympathetic innervation and perfusion. LGE CMR was conducted to assess total myocardial scar size, scar core size, and heterogenic scar size., Results: Perfusion defect size was 16.6 ± 9.9% and innervation defect size was 33.7 ± 10.8%, which resulted in an innervation-perfusion mismatch of 17.6 ± 8.9%. Total scar size, scar core size, and heterogenic scar size were 21.2 ± 8.6%, 14.7 ± 6.6%, and 6.5 ± 2.9%, respectively. No relation between scar core size and perfusion deficit size was observed (r = 0.18, P = .36). Total scar size was correlated with the innervation defect size (r = 0.52, P = .004) and the heterogenic scar zone displayed a significant correlation with the innervation-perfusion mismatch area (r = 0.67, P < .001)., Conclusions: Denerved residual viable myocardium in ischemic cardiomyopathy as observed with innervation-perfusion PET is related to the heterogenic scar zone as assessed with LGE CMR.

Unlabelled: (11)C-meta-hydroxyephedrine ((11)C-HED) kinetics in the myocardium can be quantified using a single-tissue-compartment model together with a metabolite-corrected arterial blood sampler input function (BSIF). The need for arterial blood sampling, however, limits clinical applicability. The purpose of this study was to investigate the feasibility of replacing arterial sampling with imaging-derived input function (IDIF) and venous blood samples., Methods: Twenty patients underwent 60-min dynamic (11)C-HED PET/CT scans with online arterial blood sampling. Thirteen of these patients also underwent venous blood sampling. Data were reconstructed using both 3-dimensional row-action maximum-likelihood algorithm (3DR) and a time-of-flight (TF) list-mode reconstruction algorithm. For each reconstruction, IDIF results were compared with BSIF results. In addition, IDIF results obtained with venous blood samples and with a transformed venous-to-arterial metabolite correction were compared with results obtained with arterial metabolite corrections., Results: Correlations between IDIF- and BSIF-derived K1 and VT were high (r(2) > =0.89 for 3DR and TF). Slopes of the linear fits were significantly different from 1 for K1, for both 3DR (slope = 0.94) and TF (slope = 1.06). For VT, the slope of the linear fit was different from 1 for TF (slope = 0.93) but not for 3DR (slope = 0.98). Use of venous blood data introduced a large bias in VT (r(2) = 0.96, slope = 0.84) and a small bias in K1 (r(2) = 0.99, slope = 0.98). Use of a second-order polynomial venous-to-arterial transformation was robust and greatly reduced bias in VT (r(2) = 0.97, slope = 0.99) with no effect on K1 CONCLUSION: IDIF yielded precise results for both 3DR and TF. Venous blood samples can be used for absolute quantification of (11)C-HED studies, provided a venous-to-arterial transformation is applied. A venous-to-arterial transformation enables noninvasive, absolute quantification of (11)C-HED studies., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Objective: Non-invasive imaging of myocardial perfusion, sympathetic denervation and scar size contribute to enhanced risk prediction of ventricular arrhythmias (VA). Some of these imaging parameters, however, may be intertwined as they are based on similar pathophysiology. The aim of this study was to assess the predictive role of myocardial perfusion, sympathetic denervation and scar size on the inducibility of VA in patients with ischaemic cardiomyopathy in a head-to-head fashion., Methods: 52 patients with ischaemic heart disease and left ventricular ejection fraction (LVEF) ≤35%, referred for primary prevention implantable cardioverter-defibrillator (ICD) implantation, were included. Late gadolinium-enhanced cardiovascular MRI was performed to assess LV volumes, function and scar size. Using [(15)O]H2O and [(11)C]hydroxyephedrine positron emission tomography, both resting and hyperaemic myocardial blood flow (MBF), and sympathetic innervation were assessed. After ICD implantation, an electrophysiological study (EPS) was performed and was considered positive in case of sustained VA., Results: Patients with a positive EPS (n=25) showed more severely impaired global hyperaemic MBF (p=0.003), larger sympathetic denervation size (p=0.048) and tended to have larger scar size (p=0.07) and perfusion defect size (p=0.06) compared with EPS-negative patients (n=27). No differences were observed in LV volumes, LVEF and innervation-perfusion mismatch size. Multivariable analysis revealed that impaired hyperaemic MBF was the single best independent predictor for VA inducibility (OR 0.78, 95% CI 0.65 to 0.94, p=0.007). A combination of risk markers did not yield incremental predictive value over hyperaemic MBF alone., Conclusions: Of all previously validated approaches to evaluate the arrhythmic substrate, global impaired hyperaemic MBF was the only independent predictor of VA inducibility. Moreover, a combined approach of different imaging variables did not have incremental value., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: The perfusable tissue index (PTI) is a marker of myocardial viability. Recent technological advances have made it possible to generate parametric PTI images from a single [(15)O]H(2)O PET/CT scan. The purpose of this study was to validate these parametric PTI images., Methods: The study population comprised 46 patients with documented or suspected coronary artery disease who were studied with [(15)O]H(2)O PET and late gadolinium-enhanced (LGE) cardiac magnetic resonance imaging (CMR)., Results: Of the 736 myocardial segments included, 364 showed some degree of LGE. PTI and perfusable tissue fraction (PTF) diminished with increasing LGE. The areas under the curve of the PTI and PTF, used to predict (near) transmural LGE on CMR, were 0.86 and 0.87, respectively. Optimal sensitivity and specificity were 91 % and 73 % for PTI and 69 % and 87 % for PTF, respectively., Conclusion: PTI and PTF assessed with a single [(15)O]H(2)O scan can be utilized as markers of myocardial viability in patients with coronary artery disease.

Aims: This study aimed to study the prognostic value of myocardial oxygen consumption (MVO2) and myocardial external efficiency (MEE) from 11C‐acetate positron emission tomography (PET) in cardiac amyloidosis (CA) patients. Methods and results: Forty‐eight CA patients, both transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis, and 20 controls were included. All subjects were examined with 11C‐acetate PET and echocardiography. MVO2, forward stroke volume (FSV), and left ventricular mass (LVM) were derived from 11C‐acetate PET and used to calculate MEE. CA patients were followed for survival and the prognostic impact of clinical, echocardiographic, and 11C‐acetate PET parameters was analysed. MVO2 and MEE were reduced in CA compared with controls, but without significant difference between deceased and surviving CA patients. The ratio of 11C‐acetate PET‐derived FSV and LVM was also reduced in CA and significantly lowered in deceased patients compared with survivors. In univariate analysis, New York Heart Association class, N‐terminal pro‐brain natriuretic peptide, and the 11C‐acetate PET parameters FSV/LVM and MEE were the strongest prognostic factors. Of the 11C‐acetate PET parameters, FSV/LVM was the strongest survival predictor with hazard ratio of 0.56 per 0.1 mL/g (95% confidence interval 0.39–0.81, P = 0.002) and independently prognostic in a multivariate model. MEE significantly separated deceased from surviving CA patients with the cut‐off of 15.7% (P = 0.032). Survival was significantly shorter with FSV/LVM below 0.27 mL/g (P < 0.001), also when separating AL‐ and ATTR‐CA. Conclusions: Reduced MEE was associated with shorter survival in CA patients, but FSV/LVM was the strongest survival predictor and the only independently prognostic 11C‐acetate PET parameter in multivariate analysis. [ABSTRACT FROM AUTHOR]

This dual-site study evaluated the diagnostic accuracy of the method. Pittsburgh compound (11C]PIB) positron emission tomography (PIB-PET) has shown promise as a specific and noninvasive method for the diagnosis of cardiac amyloidosis (CA). The study had 2 parts. In the initial study, 51 subjects were included, 36 patients with known CA and increased wall thickness (15 immunoglobulin light chain [AL] and 21 transthyretin [ATTR] amyloidosis) and 15 control patients (7 were nonamyloid hypertrophic and 8 healthy volunteers). Subjects underwent PIB-PET and echocardiography. Sensitivity and specificity of PIB-PET were established for 2 simple semiquantitative approaches, standardized uptake value ratio (SUVR) and retention index (RI). The second part of the study included 11 amyloidosis patients (5 AL and 6 hereditary ATTR) without increased wall thickness to which the optimal cutoff values of SUVR (>1.09) and RI (>0.037 min-1) were applied prospectively. The diagnostic accuracy of visual inspection of 11C]PIB uptake was 100% in discriminating CA patients with increased wall thickness from controls. Semiquantitative 11C]PIB uptake discriminated CA from controls with a 94% (95% confidence interval [CI]: 80% to 99%) sensitivity for both SUVR and RI and specificity of 93% (95% CI: 66% to 100%) for SUVR and 100% (95% CI: 75% to 100%) for RI. 11C]PIB uptake was significantly higher in AL-CA than in ATTR-CA patients (p < 0.001) and discriminated AL-CA from controls with 100% (95% CI: 88% to 100%) accuracy for both the semiquantitative measures. In the prospective group without increased wall thickness, RI was elevated compared to controls (p = 0.001) and 5 of 11 subjects were evaluated as 11C]PIB PET positive. In a dual-center setting, 11C]PIB PET was highly accurate in detecting cardiac involvement in the main amyloid subtypes, with 100% accuracy in AL amyloidosis. A proportion of amyloidosis patients without known cardiac involvement were 11C]PIB PET positive, indicating that the method may detect early stages of CA. [ABSTRACT FROM AUTHOR]