Objectives This study sought to relate imaging findings on positron emission tomography (PET) to adverse cardiac events in patients referred for evaluation of known or suspected cardiac sarcoidosis. ...Background Although cardiac PET is commonly used to evaluate patients with suspected cardiac sarcoidosis, the relationship between PET findings and clinical outcomes has not been reported. Methods We studied 118 consecutive patients with no history of coronary artery disease, who were referred for PET, using 18 Ffluorodeoxyglucose (FDG) to assess for inflammation and rubidium-82 to evaluate for perfusion defects (PD), following a high-fat/low-carbohydrate diet to suppress normal myocardial glucose uptake. Blind readings of PET data categorized cardiac findings as normal, positive PD or FDG, positive PD and FDG. Images were also used to identify whether findings of extra-cardiac sarcoidosis were present. Adverse events (AE)—death or sustained ventricular tachycardia (VT)—were ascertained by electronic medical records, defibrillator interrogation, patient questionnaires, and telephone interviews. Results Among the 118 patients (age 52 ± 11 years; 57% males; mean ejection fraction: 47 ± 16%), 47 (40%) had normal and 71 (60%) had abnormal cardiac PET findings. Over a median follow-up of 1.5 years, there were 31 (26%) adverse events (27 VT and 8 deaths). Cardiac PET findings were predictive of AE, and the presence of both a PD and abnormal FDG (29% of patients) was associated with hazard ratio of 3.9 (p < 0.01) and remained significant after adjusting for left ventricular ejection fraction (LVEF) and clinical criteria. Extra-cardiac FDG uptake (26% of patients) was not associated with AE. Conclusions The presence of focal PD and FDG uptake on cardiac PET identifies patients at higher risk of death or VT. These findings offer prognostic value beyond Japanese Ministry of Health and Welfare clinical criteria, the presence of extra-cardiac sarcoidosis and LVEF.
Objectives The major aim of this study is to test the hypothesis that stress cardiac magnetic resonance (CMR) imaging can provide robust prognostic value in women presenting with suspected ischemia, ...to the same extent as in men. Background Compelling evidence indicates that women with coronary artery disease (CAD) experience worse outcomes than men owing to a lack of early diagnosis and management. Numerous clinical studies have shown that stress CMR detects evidence of myocardial ischemia and infarction at high accuracy. Compared to nuclear scintigraphy, CMR is free of ionizing radiation, has high spatial resolution for imaging small hearts, and overcomes breast attenuation artifacts, which are substantial advantages when imaging women for CAD. Methods We performed stress CMR in 405 patients (168 women, mean age 58 ± 14 years) referred for ischemia assessment. CMR techniques included cine cardiac function, perfusion imaging during vasodilating stress, and late gadolinium enhancement imaging. All patients were followed for major adverse cardiac events (MACE). Results At a median follow-up of 30 months, MACE occurred in 36 patients (9%) including 21 cardiac deaths and 15 acute myocardial infarctions. In women, CMR evidence of ischemia (ISCHEMIA) demonstrated strong association with MACE (unadjusted hazard ratio: 49.9, p < 0.0001). While women with ISCHEMIA(+) had an annual MACE rate of 15%, women with ISCHEMIA(−) had very low annual MACE rate (0.3%), which was not statistically different from the low annual MACE rate in men with ISCHEMIA(−) (1.1%). CMR myocardial ischemia score was the strongest multivariable predictor of MACE in this cohort, for both women and men, indicating robust cardiac prognostication regardless of sex. Conclusions In addition to avoiding exposure to ionizing radiation, stress CMR myocardial perfusion imaging is an effective and robust risk-stratifying tool for patients of either sex presenting with possible ischemia.
Abstract Objectives The purpose of this study was to test the hypothesis that coronary microvascular function is impaired in subjects with cardiac amyloidosis. Background Effort angina is common in ...subjects with cardiac amyloidosis, even in the absence of epicardial coronary artery disease (CAD). Methods Thirty-one subjects were prospectively enrolled in this study, including 21 subjects with definite cardiac amyloidosis without epicardial CAD and 10 subjects with hypertensive left ventricular hypertrophy (LVH). All subjects underwent rest and vasodilator stress N-13 ammonia positron emission tomography and 2-dimensional echocardiography. Global left ventricular myocardial blood flow (MBF) was quantified at rest and during peak hyperemia, and coronary flow reserve (CFR) was computed (peak stress MBF/rest MBF) adjusting for rest rate pressure product. Results Compared with the LVH group, the amyloid group showed lower rest MBF (0.59 ± 0.15 ml/g/min vs. 0.88 ± 0.23 ml/g/min; p = 0.004), stress MBF (0.85 ± 0.29 ml/g/min vs. 1.85 ± 0.45 ml/g/min; p < 0.0001), and CFR (1.19 ± 0.38 vs. 2.23 ± 0.88; p < 0.0001) and higher minimal coronary vascular resistance (111 ± 40 ml/g/min/mm Hg vs. 70 ± 19 ml/g/min/mm Hg; p = 0.004). Of note, almost all subjects with amyloidosis (>95%) had significantly reduced peak stress MBF (<1.3 ml/g/min). In multivariable linear regression analyses, a diagnosis of amyloidosis, increased left ventricular mass, and age were the only independent predictors of impaired coronary vasodilator function. Conclusions Coronary microvascular dysfunction is highly prevalent in subjects with cardiac amyloidosis, even in the absence of epicardial CAD, and may explain their anginal symptoms. Further study is required to understand whether specific therapy directed at amyloidosis may improve coronary vasomotion in amyloidosis.
Objectives This investigation sought to study the incremental value of gated rubidium (Rb)-82 positron emission tomography (PET) myocardial perfusion imaging (MPI) over clinical variables for ...predicting survival and future cardiac events. Background The prognostic value of Rb-82 PET-MPI and left ventricular ejection fraction (LVEF) reserve (stress minus rest LVEF) is not well defined. Methods 1,432 consecutive patients undergoing gated rest/vasodilator stress rubidium-82 PET were followed up for at least 1 year. Of these, rest and peak stress LVEF and LVEF reserve were available in 985 patients. Cardiac events (CE) including cardiac death or nonfatal myocardial infarction and all-cause death were assessed. Results Over a mean follow-up of 1.7 ± 0.7 years, 83 (5.8%) CE and 140 (9.7%) all-cause death were observed. There was an increase in risk for both end points with an increasing percentage of abnormal and ischemic myocardium. With normal, mild, moderate, or severely ischemic scans, the observed annualized rates of CE were 0.7%, 5.5%, 5%, and 11% and of all-cause death were 3.3%, 7.2%, 6.9%, and 12.5%, respectively. In 985 patients with peak stress gated data, the observed annualized rates of CE (2.1% vs. 5.3%, p < 0.001) and all-cause death (4.3% vs. 9.2%, p < 0.001) were higher in patients with an LVEF reserve <0% compared with those with an LVEF reserve ≥0%. On Cox proportional hazards analysis, after consideration of clinical, historical, and rest LVEF information, stress PET results and LVEF reserve yielded incremental prognostic value with respect to both CE and all-cause death. Conclusions Vasodilator stress Rb-82 PET-MPI provides incremental prognostic value to historical/clinical variables and rest LVEF to predict survival free of CE and all-cause death. An increasing percentage of ischemia on PET-MPI is associated with an increase in the risk of CE and all-cause death. Left ventricular ejection fraction reserve provides significant independent and incremental value to Rb-82 MPI for predicting the risk of future adverse events.
Myocardial perfusion imaging (MPI) with PET has expanded significantly over the past decade. With the wider availability of PET scanners and the routine use of quantitative blood flow imaging, the ...clinical use of PET MPI is expected to increase further. PET MPI is a powerful tool to identify risk, to quantify risk, and to guide therapy in patients with known or suspected coronary artery disease. A large body of evidence supports the prognostic value of PET MPI and ejection fraction in intermediate- to high-risk subjects, in women, in obese individuals, and in post-coronary artery bypass grafting individuals. A normal perfusion study indicates low risk (<1% annualized rate of cardiac events of cardiac death and non-fatal myocardial infarction), while an abnormal study indicates high risk. With accurate risk stratification, high-quality images, and quantitation, PET MPI may transform the management of patients with known or suspected coronary artery disease.
Objectives This study sought to evaluate the interrelation of atherosclerotic burden, as assessed by coronary artery calcium (CAC) score and coronary vascular function, as assessed by quantitative ...estimates of coronary flow reserve (CFR), with respect to prediction of clinical outcomes. Background The contribution of coronary vascular dysfunction, atherosclerotic burden, and the 2 combined to cardiac events is unknown. Method A total of 901 consecutive patients underwent82 Rubidium myocardial perfusion imaging (MPI) positron emission tomography (PET) and CAC scan. All patients had normal MPI. The primary endpoint was a composite of major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, late revascularization, and admission for heart failure. Results At baseline, CFR decreased (2.15 ± 0.72, 2.02 ± 0.65, and 1.88 ± 0.64, p < 0.0001) with increasing levels of CAC (0, 1 to 399, and ≥400). Over a median of 1.53 years (interquartile range: 0.77 to 2.44), there were 57 MACE. Annual risk-adjusted MACE rates were higher for patients with CFR <2.0 compared with ≥2.0 (1.9 vs. 5.5%/year, p = 0.0007) but were only borderline associated with CAC (3.1%, 3.4%, and 6.2%/year for CAC of 0, 1 to 399, and ≥400, respectively; p = 0.09). Annualized adjusted MACE was increased in the presence of impaired CFR even among patients with CAC = 0 (1.4% vs. 5.2%, p = 0.03). Cox proportional hazards analysis revealed that CFR improved model fit, risk discrimination, and risk reclassification over clinical risk, whereas CAC only modestly improved model fit without improving risk discrimination or reclassification. Conclusions In symptomatic patients with normal MPI, global CFR but not CAC provides significant incremental risk stratification over clinical risk score for prediction of major adverse cardiac events.
Objectives The purpose of this study was to quantify the effects of coronary atherosclerosis morphology and extent on myocardial flow reserve (MFR). Background Although the relationship between ...coronary stenosis and myocardial perfusion is well established, little is known about the contribution of other anatomic descriptors of atherosclerosis burden to this relationship. Methods We evaluated the relationship between atherosclerosis plaque burden, morphology, and composition and regional MFR (MFRregional ) in 73 consecutive patients undergoing Rubidium-82 positron emission tomography and coronary computed tomography angiography for the evaluation of known or suspected coronary artery disease. Results Atherosclerosis was seen in 51 of 73 patients and in 107 of 209 assessable coronary arteries. On a per-vessel basis, the percentage diameter stenosis (p = 0.02) or summed stenosis score (p = 0.002), integrating stenoses in series, was the best predictor of MFRregional . Importantly, MFRregional varied widely within each coronary stenosis category, even in vessels with nonobstructive plaques (n = 169), 38% of which had abnormal MFRregional (<2.0). Total plaque length, composition, and remodeling index were not associated with lower MFR. On a per-patient basis, the modified Duke CAD (coronary artery disease) index (p = 0.04) and the number of segments with mixed plaque (p = 0.01) were the best predictors of low MFRglobal. Conclusions Computed tomography angiography descriptors of atherosclerosis had only a modest effect on downstream MFR. On a per-patient basis, the extent and severity of atherosclerosis as assessed by the modified Duke CAD index and the number of coronary segments with mixed plaque were associated with decreased MFR.
Diagnostic Accuracy of Rubidium-82 Myocardial Perfusion Imaging With Hybrid Positron Emission Tomography/Computed Tomography in the Detection of Coronary Artery Disease Uchechukwu K. Sampson, ...Sharmila Dorbala, Atul Limaye, Raymond Kwong, Marcelo F. Di Carli We evaluated the diagnostic performance of rest-stress rubidium-82 myocardial perfusion positron emission tomography-computed tomography (PET-CT) imaging in the detection of obstructive coronary artery disease (CAD) in 64 patients with suspected CAD and 38 patients with a low likelihood for CAD. The overall sensitivity, specificity, and diagnostic accuracy of rubidium-82 PET-CT were 93%, 83%, and 87% respectively. All patients with a low likelihood for CAD showed normal scans, for a normalcy rate of 100%. The sensitivity for detecting CAD was equally high in patients with single and multivessel disease, in men and women, and in obese and nonobese individuals.
Abstract Background Hodgkin lymphoma (HL) survivors treated with thoracic radiation therapy (RT) have impaired exercise tolerance and increased cardiovascular mortality. Objectives The purpose of ...this study was to evaluate the prevalence of autonomic dysfunction and its implications on exercise capacity and mortality in long-term survivors of HL. Methods Exercise parameters in 263 HL survivors referred for exercise treadmill testing at a median interval of 19 years after RT were compared with 526 age-, sex-, and cardiovascular risk score–matched control subjects. Within the RT cohort, the presence of autonomic dysfunction, defined by an elevated resting heart rate (HR) (≥80 beats/min) and abnormal heart rate recovery (HRR) at 1 min (≤12 beats/min if active cool-down, or ≤18 beats/min if passive recovery), was correlated with exercise capacity and all-cause mortality over a median follow-up of 3 years. Results RT was associated with elevated resting HR and abnormal HRR after adjusting for age, sex, cardiovascular risk factors, medications, and indication for exercise treadmill testing: odds ratio: 3.96 (95% confidence interval CI: 2.52 to 6.23) and odds ratio: 5.32 (95% CI: 2.94 to 9.65), respectively. Prevalence of autonomic dysfunction increased with radiation dose and time from RT. Both elevated resting HR and abnormal HRR were associated with reduced exercise capacity in RT patients. Abnormal HRR was also associated with increased all-cause mortality (age-adjusted hazard ratio: 4.60 95% CI: 1.62 to 13.02). Conclusions Thoracic RT is associated with autonomic dysfunction, as measured by elevated resting HR and abnormal HRR. These abnormalities are associated with impaired exercise tolerance, and abnormal HRR predicts increased all-cause mortality in RT patients.
Right Ventricular Dysfunction Assessed by Cardiovascular Magnetic Resonance Imaging Predicts Poor Prognosis Late After Myocardial Infarction Eric Larose, Peter Ganz, H. Glenn Reynolds, Sharmila ...Dorbala, Marcelo F. Di Carli, Kenneth A. Brown, Raymond Y. Kwong We investigated whether right ventricular (RV) function late after myocardial infarction (MI) predicts long-term prognosis. Right ventricular ejection fraction (RVEF) was assessed by using cardiovascular magnetic resonance imaging in 147 patients late after MI. A total of 26 deaths occurred during a median follow-up of 17 months. RVEF predicted mortality independently of patient age, left ventricular (LV) infarct size, and LV ejection fraction. Quantitation of RVEF by cardiovascular magnetic resonance imaging is valuable for risk-stratifying patients after MI beyond traditional prognostic factors.
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