Assessment of myocardial viability with [15O]water PET: A validation study in experimental myocardial infarction.

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.

Computed tomography versus invasive coronary angiography: design and methods of the pragmatic randomised multicentre DISCHARGE trial.

OBJECTIVES: More than 3.5 million invasive coronary angiographies (ICA) are performed in Europe annually. Approximately 2 million of these invasive procedures might be reduced by noninvasive tests because no coronary intervention is performed. Computed tomography (CT) is the most accurate noninvasive test for detection and exclusion of coronary artery disease (CAD). To investigate the comparative effectiveness of CT and ICA, we designed the European pragmatic multicentre DISCHARGE trial funded by the 7th Framework Programme of the European Union (EC-GA 603266). METHODS: In this trial, patients with a low-to-intermediate pretest probability (10-60 %) of suspected CAD and a clinical indication for ICA because of stable chest pain will be randomised in a 1-to-1 ratio to CT or ICA. CT and ICA findings guide subsequent management decisions by the local heart teams according to current evidence and European guidelines. RESULTS: Major adverse cardiovascular events (MACE) defined as cardiovascular death, myocardial infarction and stroke as a composite endpoint will be the primary outcome measure. Secondary and other outcomes include cost-effectiveness, radiation exposure, health-related quality of life (HRQoL), socioeconomic status, lifestyle, adverse events related to CT/ICA, and gender differences. CONCLUSIONS: The DISCHARGE trial will assess the comparative effectiveness of CT and ICA. KEY POINTS: • Coronary artery disease (CAD) is a major cause of morbidity and mortality. • Invasive coronary angiography (ICA) is the reference standard for detection of CAD. • Noninvasive computed tomography angiography excludes CAD with high sensitivity. • CT may effectively reduce the approximately 2 million negative ICAs in Europe. • DISCHARGE addresses this hypothesis in patients with low-to-intermediate pretest probability for CAD.

Cardiac remodeling in a new pig model of chronic heart failure: Assessment of left ventricular functional, metabolic, and structural changes using PET, CT, and echocardiography.

AIMS: Large animal models are needed to study disease mechanisms in heart failure (HF). In the present study we characterized the functional, metabolic, and structural changes of myocardium in a novel pig model of chronic myocardial infarction (MI) by using multimodality imaging and histology. METHODS AND RESULTS: Male farm pigs underwent a two-step occlusion of the left anterior descending coronary artery with concurrent distal ligation and implantation of a proximal ameroid constrictor (HF group), or sham operation (control group). Three months after the operation, cardiac output and wall stress were measured by echocardiography. Left ventricle (LV) volumes and mass were measured by computed tomography (CT). Myocardial perfusion was evaluated by [(15)O]water and oxygen consumption using [(11)C]acetate positron emission tomography, and the efficiency of myocardial work was calculated. Histological examinations were conducted to detect MI, hypertrophy, and fibrosis. Animals in the HF group had a large anterior MI scar. CT showed larger LV diastolic volume and lower ejection fraction in HF pigs than in controls. Perfusion and oxygen consumption in the remote non-infarcted myocardium were preserved in HF pigs as compared to controls. Global LV work and efficiency were significantly lower in HF than control pigs and was associated with increased wall stress. Histology showed myocyte hypertrophy but not increased interstitial fibrosis in the remote segments in HF pigs. CONCLUSIONS: The chronic post-infarction model of HF is suitable for studies aimed to evaluate LV remodeling and changes in oxidative metabolism and can be useful for testing new therapies for HF.

Quantitative assessment of myocardial perfusion in the detection of significant coronary artery disease: cutoff values and diagnostic accuracy of quantitative [(15)O]H2O PET imaging.

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 [(15)O]H2O positron emission tomography (PET). METHODS: A total of 330 patients underwent both quantitative [(15)O]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 [(15)O]H2O PET provided high diagnostic performance, but both sex and age should be taken into account.

Transthoracic echocardiography for non-invasive assessment of coronary vasodilator function after DES implantation.

AIMS: Coronary vasodilator dysfunction has been reported after drug-eluting stent (DES) implantation. Recent ESC guidelines suggest that transthoracic echocardiography (TTE) may be considered for assessment of coronary flow reserve (CFR) and microvascular disease in patients with stable angina, but its reliability has not been tested in patients with DES. We sought to assess the agreement between TTE (CFRTTE) and invasive thermodilution-derived CFR (CFRThermodilution) as well as their association with index of microcirculatory resistance (IMR) in mid-term follow-up after percutaneous coronary intervention for acute coronary syndrome. METHODS AND RESULTS: CFRTTE and CFRThermodilution were assessed 3 months after DES implantation in the left anterior descending artery in 24 patients. Patients with haemodynamically significant epicardial stenosis (fractional flow reserve <0.75) were excluded. Correlation between the two methods was good (r = 0.71, P < 0.001), but CFRThermodilution (mean ± SD) tended to be higher (3.17 ± 1.00 vs. 2.87 ± 0.72; mean difference 0.29, 95% confidence interval -0.06 to 0.59). In Bland-Altman analysis, there was a trend towards a greater difference in the range of higher invasive values. Nevertheless, TTE was successful in discriminating moderately impaired CFR (≤2.5) (P = 0.001) and severely impaired CFR (≤2.0) (P < 0.001) when compared with an invasive method. No association between either CFR measurements vs. IMR measurement was detected, suggesting that in addition to microcirculatory function, CFR also accounts for epicardial vasodilator function in the absence of haemodynamically significant stenosis. CONCLUSION: TTE is a feasible and reliable method for the assessment of CFR and vasodilator dysfunction after DES implantation. Values obtained with this method successfully find abnormal CFR confirmed with the invasive thermodilution method.