Benjamin J Chow

Prognostic Value of Noninvasive Cardiovascular Testing in Patients with Stable Chest Pain: Insights from the Promise Trial

Background: Optimal management of patients with stable chest pain relies on the prognostic information provided by noninvasive cardiovascular testing, but there are limited data from randomized trials comparing anatomic with functional testing. Methods: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain and intermediate pretest probability for obstructive coronary artery disease (CAD) were randomly assigned to functional testing (exercise electrocardiography, nuclear stress, or stress echocardiography) or coronary computed tomography angiography (CTA). Site-based diagnostic test reports were classified as normal or mildly, moderately, or severely abnormal. The primary end point was death, myocardial infarction, or unstable angina hospitalizations over a median follow-up of 26.1 months. Results: Both the prevalence of normal test results and incidence rate of events in these patients were significantly lower among 4500 patients randomly assigned to CTA in comparison with 4602 patients randomly assigned to functional testing (33.4% versus 78.0%, and 0.9% versus 2.1%, respectively; both P<0.001). In CTA, 54.0% of events (n=74/137) occurred in patients with nonobstructive CAD (1%–69% stenosis). Prevalence of obstructive CAD and myocardial ischemia was low (11.9% versus 12.7%, respectively), with both findings having similar prognostic value (hazard ratio, 3.74; 95% confidence interval [CI], 2.60–5.39; and 3.47; 95% CI, 2.42–4.99). When test findings were stratified as mildly, moderately, or severely abnormal, hazard ratios for events in comparison with normal tests increased proportionally for CTA (2.94, 7.67, 10.13; all P<0.001) but not for corresponding functional testing categories (0.94 [P=0.87], 2.65 [P=0.001], 3.88 [P<0.001]). The discriminatory ability of CTA in predicting events was significantly better than functional testing (c-index, 0.72; 95% CI, 0.68–0.76 versus 0.64; 95% CI, 0.59–0.69; P=0.04). If 2714 patients with at least an intermediate Framingham Risk Score (>10%) who had a normal functional test were reclassified as being mildly abnormal, the discriminatory capacity improved to 0.69 (95% CI, 0.64–0.74). Conclusions: Coronary CTA, by identifying patients at risk because of nonobstructive CAD, provides better prognostic information than functional testing in contemporary patients who have stable chest pain with a low burden of obstructive CAD, myocardial ischemia, and events. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01174550.

Recent advances in cardiac imaging for patients with heart failure

PURPOSE OF REVIEW Transthoracic echocardiography (ECHO) and single-photon emission computed tomography (SPECT) are routine in many heart failure patients. Recently, other imaging tests have emerged in heart failure management: cardiovascular magnetic resonance (CMR), positron emission tomography (PET) and computed tomography (CT). This article reviews recent developments in heart failure imaging. RECENT FINDINGS Longitudinal left ventricular systolic strain on ECHO speckle tracking imaging detects subclinical cardiomyopathy and predicts survival in symptomatic heart failure. Late gadolinium enhancement for myocardial scar is an independent predictor of death or transplantation in ischemic and nonischemic cardiomyopathy. In contrast to earlier reports, both ECHO and CMR contrast have a negligible risk of adverse outcomes. Stress perfusion imaging (SPECT or PET) and PET flow quantification have prognostic value in ischemic cardiomyopathy. F-2-fluoro-2-deoxyglucose (FDG) PET directed management can impact outcome. Abnormal myocardial neuronal activity on I-metaiodobenzylguanidine (MIBG) imaging is associated with increased risk of ventricular arrhythmias and death. Cardiac CT potentially could assess heart failure etiology through coronary angiography and myocardial tissue characterization but its precise role remains undetermined. SUMMARY There have been several exciting developments in all imaging modalities. Large multicenter trials such as IMAGE heart failure are required to standardize measures and establish benefit before widespread use in heart failure can be recommended.

Cardiac PET: metabolic and functional imaging of the myocardium.

Cardiac PET has evolved over the past 30 years to gain wider acceptance as a valuable modality for a variety of cardiac conditions. Wider availability of scanners as well as changes in reimbursement policies in more recent years has further increased its use. Moreover, with the emergence of novel radionuclides as well as further advances in scanner technology, the use of cardiac PET can be expected to increase further in both clinical practice and the research arena. PET has demonstrated superior diagnostic accuracy for the diagnosis of coronary artery disease in comparison with single-photon emission tomography while it provides robust prognostic value. The addition of absolute flow quantification increases sensitivity for 3-vessel disease as well as providing incremental functional and prognostic information. Metabolic imaging using (18)F-fluorodeoxyglucose can be used to guide revascularization in the setting of heart failure and also to detect active inflammation in conditions such as cardiac sarcoidosis and within atherosclerotic plaque, improving our understanding of the processes that underlie these conditions. However, although the pace of new developments is rapid, there remains a gap in evidence for many of these advances and further studies are required.

Long-Term Follow-Up of Outcomes With F-18-Fluorodeoxyglucose Positron Emission Tomography Imaging–Assisted Management of Patients With Severe Left Ventricular Dysfunction Secondary to Coronary Disease

Background—Whether viability imaging can impact long-term patient outcomes is uncertain. The PARR-2 study (Positron Emission Tomography and Recovery Following Revascularization) showed a nonsignificant trend toward improved outcomes at 1 year using an F-18-fluorodeoxyglucose positron emission tomography (PET)–assisted strategy in patients with suspected ischemic cardiomyopathy. When patients adhered to F-18-fluorodeoxyglucose PET recommendations, outcome benefit was observed. Long-term outcomes of viability imaging–assisted management have not previously been evaluated in a randomized controlled trial. Methods and Results—PARR-2 randomized patients with severe left ventricular dysfunction and suspected CAD being considered for revascularization or transplantation to standard care (n= 195) versus PET-assisted management (n=197) at sites participating in long-term follow-up. The predefined primary outcome was time to composite event (cardiac death, myocardial infarction, or cardiac hospitalization). After 5 years, 105 (53%) patients in the PET arm and 111 (57%) in the standard care arm experienced the composite event (hazard ratio for time to composite event =0.82 [95% confidence interval 0.62–1.07]; P=0.15). When only patients who adhered to PET recommendations were included, the hazard ratio for the time to primary outcome was 0.73 (95% confidence interval 0.54–0.99; P=0.042). Conclusions—After a 5-year follow-up in patients with left ventricular dysfunction and suspected CAD, overall, PET-assisted management did not significantly reduce cardiac events compared with standard care. However, significant benefits were observed when there was adherence to PET recommendations. PET viability imaging may be best applied when there is likely to be adherence to imaging-based recommendations. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00385242.

Does FDG PET-Assisted Management of Patients With Left Ventricular Dysfunction Improve Quality of Life? A Substudy of the PARR-2 Trial

BACKGROUND Patients with left ventricular dysfunction whose management is directed by F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging may have a quality of life (QOL) benefit over standard care. METHODS Among 430 patients randomized in the PET and Recovery Following Revascularization (PARR)-2 trial to FDG PET-assisted management vs standard, QOL scores were obtained using the European Quality of Life-5 Dimensions (EQ-5D) in 427 patients at baseline (FDG PET n = 216; standard n = 211) and 355 patients at 12-month follow-up (FDG PET n = 184; standard n = 171). EQ-5D scores between FDG PET and standard arms were compared using mixed model repeated measures (MMRM). Subgroup analysis compared EQ-5D scores between patients in FDG PET who adhered to PET recommendations (Adherence) vs standard using MMRM. Interaction of revascularization with management was assessed using a general linear model. RESULTS A trend toward higher EQ-5D scores in FDG PET was observed (P = 0.056). Subgroup analysis showed a significant difference favouring adherence (P = 0.04). Higher QOL at 6 months for FDG PET (P = 0.02) and Adherence (P = 0.02) were observed. For revascularization, an interaction with management (FDG PET vs standard) for QOL was observed (6 months: P = 0.01; 12 months: P = 0.1); Adherence (6 months: P = 0.01; 12 months: P = 0.1). CONCLUSIONS FDG PET-directed management improves QOL, at least in the short-term and with adherence to recommendations. This may relate to revascularization, and may indicate better treatment selection using FDG PET.

Obesity and the Challenges of Noninvasive Imaging for the Detection of Coronary Artery Disease

Obesity is a significant health problem that could potentially lead to increased cardiovascular risk. Noninvasive imaging plays an important role in the evaluation of cardiovascular symptoms and risk of these patients. Selection of the appropriate test in the diagnosis of obstructive coronary artery disease in this unique population is important. In this article, we focus on the strengths, limitations, and recommendations of the various noninvasive cardiac imaging modalities available in the detection of obstructive coronary artery disease. We have suggested an algorithm to help direct investigation. Ultimately, patient management should be individualized based on clinical judgement, test availability, and local expertise.

Quantification of myocardial blood flow using PET to improve the management of patients with stable ischemic coronary artery disease

Cardiac PET has been evolving over the past 30 years. Today, it is accepted as a valuable imaging modality for the noninvasive assessment of coronary artery disease. PET has demonstrated superior diagnostic accuracy for the detection of coronary artery disease compared with single-photon emission computed tomography, and also has a well-established prognostic value. The routine addition of absolute quantification of myocardial blood flow increases the diagnostic accuracy for three-vessel disease and provides incremental functional and prognostic information. Moreover, the characterization of the vasodilator capacity of the coronary circulation may guide proper decision-making and monitor the effects of lifestyle changes, exercise training, risk factor modification or medical therapy for improving regional and global myocardial blood flow. This type of image-guided approach to individualized patient therapy is now attainable with the routine use of cardiac PET flow reserve imaging.

Imaging the failing right ventricle.

Purpose of review This article will review the noninvasive modalities currently available for imaging the right ventricle, including two-dimensional echocardiography, cardiac magnetic resonance (CMR), multidetector computed tomography (MDCT), radionuclide ventriculography (RNV) and PET. Recent findings Improvements in established imaging techniques, as well as development of newer imaging modalities, have shed light on the right ventricles adaptation to pressure and volume overload states and have allowed better prognostication in patients with right ventricular failure (RVF). Summary As therapies are developed to alter the natural history of RVF, a better understanding of the imaging modalities for the assessment of right ventricular morphology and function is needed. This review will provide an approach to investigating the patient with suspected RVF and highlight the strengths and weakness of each imaging modality.

Cardiac CT assessment of left ventricular mass in mid-diastasis and its prognostic value.

Aims To determine the influence of cardiac motion on measurements of left ventricular (LV) mass obtained with 64-slice computed tomography (CT) and to elucidate the prognostic value of LV mass on major adverse cardiac events (MACE) and all-cause mortality. Increased LV mass has been linked with MACE. Although Cardiac CT allows measurement of LV anatomy, it is susceptible to motion artefacts often requiring image acquisition during diastasis. There is a need to understand variability in LV mass measurements across phases of the cardiac cycle, and whether mid-diastolic measurements have prognostic value. Methods and results The study comprised two equally sized cohorts of patients that had undergone retrospectively gated cardiac CT: patients who had MACE and/or all-cause death at follow-up and a matched (age, sex, and risk factors) event-free cohort. LV mass was measured at mid-diastole, end-diastole, and end-systole. Correlation and agreement between phases were determined. The incremental value of mid-diastolic hypertrophy (LVH) over the National Cholesterol Education Programme (NCEP) risk was performed for LV mass indices normalized to body surface area (LVMIBSA) or weight (LVMIWeight). Of 166 patients, 31.3% experienced MACE and 28.9% died of any cause (follow-up 22.9 ± 13.4 months). LV mass at all cardiac phases were strongly correlated (r > 0.94). Mean mid-diastolic LVMIBSA was higher in the cohort with events (93.7 vs. 80.7 g/m2, P= 0.008) as was LVMIWeight (2.26 vs. 1.88 g/kg, P = 0.001). LVMIBSA and LVMIWeight had prognostic value incremental to NCEP with 1.85 and 2.47 hazard ratios, respectively. Conclusions Measurement of LV mass can be obtained by cardiac CT images obtained at mid-diastasis. LV mass measurements obtained at mid-diastasis have prognostic value.

Identification of Inflamed Aortic Plaque in Conventional Fluorodeoxyglucose–Positron Emission Tomography Myocardial Viability Studies

BACKGROUND It has been shown that (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is useful in identifying inflamed plaque in major arteries. This study evaluated the feasibility of inflamed plaque detection with routinely acquired cardiac FDG-PET viability studies in patients with severe coronary artery disease and left ventricular dysfunction. METHODS Clinically indicated myocardial viability scans using FDG and PET combined with computed tomography from 103 patients were retrospectively analyzed for FDG uptake in the proximal, ascending, and descending thoracic aorta. Aortic uptake was graded on the basis of peak and mean target-to-background ratio (TBR): grade 0, < 1; grade 1, 1.01-1.49; grade 2, 1.5-1.99; and grade 3, > 2. RESULTS Of the 103 patients, 71 (68.9%) had a history of myocardial infarction, 88 (85.4%) were on statins, and 70 (68%) were on angiotensin-converting enzyme (ACE) inhibitors. Increased FDG uptake (mean TBR grade 1-3) was seen in 79 of 103 patients (77%), and grade 3 aortic uptake based on peak TBR was found in 12 of 103 patients (12%). CONCLUSIONS Detection of inflamed atherosclerotic plaque in the aorta with conventional FDG viability scans is feasible. The rate of very positive uptake in this population of ischemic heart disease patients is low, possibly reflecting aggressive secondary risk factor modification including statin and ACE inhibitor use.