Rob S. Beanlands

Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making.

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology-pressure and flow-as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements.

Prognostic Value of 64-Slice Cardiac Computed Tomography: Severity of Coronary Artery Disease, Coronary Atherosclerosis, and Left Ventricular Ejection Fraction

OBJECTIVES We sought to determine the prognostic and incremental value of coronary artery disease (CAD) severity, coronary atherosclerosis, and left ventricular ejection fraction (LVEF) measured with cardiac computed tomography angiography (CTA). BACKGROUND CTA is an emerging tool used for the detection of obstructive CAD. However, there are limited data supporting the prognostic value of 64-slice CTA and its ability to predict all-cause mortality and major adverse cardiac events such as cardiac death and nonfatal myocardial infarction. METHODS Consecutive patients (without history of revascularization, heart transplantation, and congenital heart disease) were prospectively enrolled. Each CTA was evaluated for CAD severity, total plaque score, and LVEF. Patients were followed, and all events were confirmed with death certificates or hospital or physician records and reviewed by a clinical events committee. RESULTS Between February 2006 and February 2008, 2,076 consecutive patients were prospectively enrolled and followed for a mean of 16 +/- 8 months. At follow-up, a total of 31 (1.5%) patients had cardiac death or nonfatal myocardial infarction and 47 (2.3%) had all-cause mortality or nonfatal myocardial infarction. Multivariate analysis showed that CAD severity (hazard ratio [HR]: 3.02; 95% confidence interval [CI]: 1.89 to 4.83) was a predictor of major adverse cardiac events and that LVEF (HR: 1.47; 95% CI: 1.17 to 1.86) had incremental value over CAD severity. Total plaque score had incremental value over CAD severity and LVEF for all-cause mortality and nonfatal myocardial infarction (HR: 1.17; 95% CI: 1.06 to 1.29). CONCLUSIONS Using CTA, CAD severity, LVEF, and total plaque score seems to have prognostic and incremental value over routine clinical predictors. Cardiac CTA seems to be a promising noninvasive modality with prognostic value.

Quantification of myocardial blood flow with 82Rb dynamic PET imaging

PurposeThe PET tracer 82Rb is commonly used to evaluate regional perfusion defects for the diagnosis of coronary artery disease. There is limited information on the quantification of myocardial blood flow and flow reserve with this tracer. The goal of this study was to investigate the use of a one-compartment model of 82Rb kinetics for the quantification of myocardial blood flow.MethodsFourteen healthy volunteers underwent rest and dipyridamole stress imaging with both 13N-ammonia and 82Rb within a 2-week interval. Myocardial blood flow was estimated from the time-activity curves measured with 13N-ammonia using a standard two-compartment model. The uptake parameter of the one-compartment model was estimated from the time-activity curves measured with 82Rb. To describe the relationship between myocardial blood flow and the uptake parameter, a nonlinear extraction function was fitted to the data. This function was then used to convert estimates of the uptake parameter to flow estimates. The extraction function was validated with an independent data set obtained from 13 subjects with documented evidence of coronary artery disease (CAD).ResultsThe one-compartment model described 82Rb kinetics very well (median R-square = 0.98). The flow estimates obtained with 82Rb were well correlated with those obtained with 13N-ammonia (r = 0.85), and the best-fit line did not differ significantly from the identity line. Data obtained from the subjects with CAD confirmed the validity of the estimated extraction function.ConclusionIt is possible to obtain accurate estimates of myocardial blood flow and flow reserve with a one-compartment model of 82Rb kinetics and a nonlinear extraction function.

The Use of 18F-FDG PET in the Diagnosis of Cardiac Sarcoidosis: A Systematic Review and Metaanalysis Including the Ontario Experience

Cardiac sarcoidosis is a potentially fatal complication of sarcoidosis. The 1993 guidelines of the Ministry of Health, Labour, and Welfare (MHLW) of Japan have been used as the diagnostic gold standard and for comparison with imaging modalities. 18F-FDG PET is not currently included in the guidelines. However, studies have shown promising data using 18F-FDG PET. We conducted a systematic review of studies that evaluated the accuracy of 18F-FDG PET for the diagnosis of cardiac sarcoidosis compared with MHLW guidelines. Data from a prospective Ontario provincial registry are also reported and included in the metaanalysis. Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies that satisfied predetermined criteria. Quality evaluation using the Quality Assessment for Diagnostic Accuracy Studies was performed by 2 independent masked observers. Data were extracted and analyzed to measure study-specific and pooled accuracy for 18F-FDG PET compared with the MHLW as the reference. Results: A total of 519 titles was identified; 7 studies, including the Ontario registry, were selected for inclusion. Metaanalysis of these 7 studies was conducted, with a total of 164 patients, most of whom had been diagnosed with systemic sarcoidosis. The prevalence of cardiac sarcoidosis was 50% in the whole population. Pooled estimates for 18F-FDG PET yielded 89% sensitivity (95% confidence interval [CI], 79%–96%), 78% specificity (95% CI, 68%–86%), a 4.1 positive likelihood ratio (95% CI, 1.7–10), and a 0.19 negative likelihood ratio (95% CI, 0.1–0.4). The overall diagnostic odds ratio was 25.6 (95% CI, 7.3–89.5), and the area under the summary receiver operator characteristic curve was 93% ± 3.5. The Ontario study yielded sensitivity and specificity of 79% and 70%, respectively. Conclusion: The high diagnostic accuracy determined for 18F-FDG PET in this metaanalysis suggests potential value for diagnosis of cardiac sarcoidosis compared with the MHLW guidelines. These results may affect patient care by providing supportive evidence for more effective use of 18F-FDG PET in the diagnosis of cardiac sarcoidosis. Large-scale multicenter studies are required to further evaluate this role.

Evaluation of simulation-based scatter correction for 3-D PET cardiac imaging

Quantitative imaging of the human thorax poses one of the most difficult challenges for three-dimensional (3-D) (septaless) positron emission tomography (PET), due to the strong attenuation of the annihilation radiation and the large contribution of scattered photons to the data. In [/sup 18/F] fluorodeoxyglucose (FDG) studies of the heart with the patients arms in the field of view, the contribution of scattered events can exceed 50% of the total detected coincidences. Accurate correction for this scatter component is necessary for meaningful quantitative image analysis and tracer kinetic modeling. For this reason, the authors have implemented a single-scatter simulation technique for scatter correction in positron volume imaging. Here, they describe this algorithm and present scatter correction results from human and chest phantom studies.

Effect of Cardiac Resynchronization on Myocardial Efficiency and Regional Oxidative Metabolism

Background—Recent studies have demonstrated increased left ventricular contractility with cardiac resynchronization therapy (CRT) using atriobiventricular stimulation. This study evaluated the effect of CRT on myocardial oxidative metabolism and efficiency. Methods and Results—Eight patients with New York Heart Association functional class III-IV congestive heart failure were studied during atrial pacing (control) and atriobiventricular stimulation at the same rate. The monoexponential clearance rate of [11C]acetate (kmono) was measured with positron emission tomography to assess myocardial oxidative metabolism in the left and right ventricles (LV and RV, respectively). Myocardial efficiency was measured using the work metabolic index (WMI). Stroke volume index improved by 10% (P =0.011) with CRT, although both global LV and RV kmono were unchanged compared with control. Septal kmono increased by 15% (P =0.04), and the septal/lateral wall kmono ratio increased by 22% (P =0.01). WMI increased by 13% (P =0.024) with CRT. Conclusions—CRT improves LV function without increasing global LV oxidative metabolism, resulting in improved myocardial efficiency. Oxidative metabolism of the interventricular septum increases relative to the lateral wall, which suggests successful resynchronization.

Projected Valve Area at Normal Flow Rate Improves the Assessment of Stenosis Severity in Patients With Low-Flow, Low-Gradient Aortic Stenosis The Multicenter TOPAS (Truly or Pseudo-Severe Aortic Stenosis) Study

Background— We sought to investigate the use of a new parameter, the projected effective orifice area (EOAproj) at normal transvalvular flow rate (250 mL/s), to better differentiate between truly severe (TS) and pseudo-severe (PS) aortic stenosis (AS) during dobutamine stress echocardiography (DSE). Changes in various parameters of stenosis severity have been used to differentiate between TS and PS AS during DSE. However, the magnitude of these changes lacks standardization because they are dependent on the variable magnitude of the transvalvular flow change occurring during DSE. Methods and Results— The use of EOAproj to differentiate TS from PS AS was investigated in an in vitro model and in 23 patients with low-flow AS (indexed EOA <0.6 cm2/m2, left ventricular ejection fraction ≤40%) undergoing DSE and subsequent aortic valve replacement. For an individual valve, EOA was plotted against transvalvular flow (Q) at each dobutamine stage, and valve compliance (VC) was derived as the slope of the regression line fitted to the EOA versus Q plot; EOAproj was calculated as EOAproj=EOArest+VC×(250−Qrest), where EOArest and Qrest are the EOA and Q at rest. Classification between TS and PS was based on either response to flow increase (in vitro) or visual inspection at surgery (in vivo). EOAproj was the most accurate parameter in differentiating between TS and PS both in vitro and in vivo. In vivo, 15 of 23 patients (65%) had TS and 8 of 23 (35%) had PS. The percentage of correct classification was 83% for EOAproj and 91% for indexed EOAproj compared with percentages of 61% to 74% for the other echocardiographic parameters usually used for this purpose. Conclusions— EOAproj provides a standardized evaluation of AS severity with DSE and improves the diagnostic accuracy for distinguishing TS and PS AS in patients with low-flow, low-gradient AS.

Patient management after noninvasive cardiac imaging: Results from SPARC (Study of myocardial perfusion and coronary anatomy imaging roles in coronary artery disease)

OBJECTIVES This study examined short-term cardiac catheterization rates and medication changes after cardiac imaging. BACKGROUND Noninvasive cardiac imaging is widely used in coronary artery disease, but its effects on subsequent patient management are unclear. METHODS We assessed the 90-day post-test rates of catheterization and medication changes in a prospective registry of 1,703 patients without a documented history of coronary artery disease and an intermediate to high likelihood of coronary artery disease undergoing cardiac single-photon emission computed tomography, positron emission tomography, or 64-slice coronary computed tomography angiography. RESULTS Baseline medication use was relatively infrequent. At 90 days, 9.6% of patients underwent catheterization. The rates of catheterization and medication changes increased in proportion to test abnormality findings. Among patients with the most severe test result findings, 38% to 61% were not referred to catheterization, 20% to 30% were not receiving aspirin, 35% to 44% were not receiving a beta-blocker, and 20% to 25% were not receiving a lipid-lowering agent at 90 days after the index test. Risk-adjusted analyses revealed that compared with stress single-photon emission computed tomography or positron emission tomography, changes in aspirin and lipid-lowering agent use was greater after computed tomography angiography, as was the 90-day catheterization referral rate in the setting of normal/nonobstructive and mildly abnormal test results. CONCLUSIONS Overall, noninvasive testing had only a modest impact on clinical management of patients referred for clinical testing. Although post-imaging use of cardiac catheterization and medical therapy increased in proportion to the degree of abnormality findings, the frequency of catheterization and medication change suggests possible undertreatment of higher risk patients. Patients were more likely to undergo cardiac catheterization after computed tomography angiography than after single-photon emission computed tomography or positron emission tomography after normal/nonobstructive and mildly abnormal study findings. (Study of Perfusion and Anatomys Role in Coronary Artery [CAD] [SPARC]; NCT00321399).

Positron emission tomography and recovery following revascularization (PARR-1): the importance of scar and the development of a prediction rule for the degree of recovery of left ventricular function.

OBJECTIVES The aim of this study was to determine whether the extent of viability or scar is important in the amount of recovery of left ventricular (LV) function, and to develop a model for predicting recovery after revascularization that could be tested in a randomized trial. BACKGROUND F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) is used to define viable myocardium in patients with coronary artery disease (CAD) and severe LV dysfunction and to guide revascularization decisions. Whether this approach improves clinical outcomes has not been tested in a randomized trial. Before doing so, an objective model for prediction of recovery is required. METHODS A total of 82 patients with CAD and an ejection fraction (EF) < or =35% had FDG PET perfusion imaging before revascularization. Complete follow-up was available on 70 patients (86%). Patients had radionuclide angiograms at baseline and three months post-revascularization. RESULTS Diabetes (p = 0.029), time to operation (p = 0.008), and scar score (p = 0.001) were significant independent predictors of the change in EF. Previous coronary artery bypass graft confounded the effect of age. There was a significant interaction between the perfusion tracer used and mismatch score (p = 0.02). The multivariable prediction model incorporating PET and clinical variables had a goodness of fit with p = 0.001. Across tertiles of scar scores (I, small: 0% to 16%; II, moderate: 16% to 27.5%; III, large: 27.5% to 47%), the changes in EFs were 9.0 +/- 1.9%, 3.7 +/- 1.6%, and 1.3 +/- 1.5% (p = 0.003: I vs. III), respectively. CONCLUSIONS In patients with severe LV dysfunction, the amount of scar was a significant independent predictor of LV function recovery after revascularization. A combination of PET and clinical parameters predicts the degree of recovery. This model is being applied in a large randomized controlled trial to determine the effectiveness of therapy guided by FDG PET.

Predictors of Outcomes in Low-Flow, Low-Gradient Aortic Stenosis Results of the Multicenter TOPAS Study

Background— Patients with low-flow, low-gradient aortic stenosis have a poor prognosis with conservative therapy but a high operative mortality if treated surgically. Recently, we proposed a new index of aortic stenosis severity derived from dobutamine stress echocardiography, the projected aortic valve area at a normal transvalvular flow rate, as superior to other conventional indices to differentiate true-severe from pseudosevere aortic stenosis. The objective of this study was to identify the determinants of survival, functional status, and change in left ventricular ejection fraction during follow-up of patients with low-flow, low-gradient aortic stenosis. Methods and Results— One hundred one patients with low-flow, low-gradient aortic stenosis (aortic valve area ≤1.2 cm2, left ventricular ejection fraction ≤40%, and mean gradient ≤40 mm Hg) underwent dobutamine stress echocardiography and an assessment of functional capacity using the Duke Activity Status Index. A subset of 72 patients also underwent a 6-minute walk test. Overall survival was 70±5% at 1 year and 57±6% at 3 years. After adjusting for age, gender, and the type of treatment (aortic valve replacement versus no aortic valve replacement), significant predictors of mortality during follow-up were a Duke Activity Status Index ≤20 (P=0.0005) or 6-minute walk test distance ≤320 m (P<0.0001, in the subset of 72 patients), projected aortic valve area at a normal transvalvular flow rate ≤1.2 cm2 (P=0.03), and peak dobutamine stress echocardiography left ventricular ejection fraction ≤35% (P=0.03). More severe stenosis, defined as projected aortic valve area ≤1.2 cm2, was a predictor of mortality only in the no aortic valve replacement group. The Duke Activity Status Index, 6-minute walk test, and left ventricular ejection fraction improved significantly during follow-up in the aortic valve replacement group, but remained unchanged or decreased in the no aortic valve replacement group. Conclusion— In patients with low-flow, low-gradient aortic stenosis, the most significant risk factors for poor outcome were (1) impaired functional capacity as measured by Duke Activity Status Index or 6-minute walk test distance; (2) more severe valve stenosis as measured by projected aortic valve area at a normal transvalvular flow rate; and (3) reduced peak stress left ventricular ejection fraction, a composite measure accounting for both resting left ventricular function and contractile reserve.