Performance of cardiac PET/CT with and without phase analysis for detection of scar in cardiac sarcoidosis: Comparison to cardiac magnetic resonance imaging.

BACKGROUND: The presence of myocardial scar in CS patients results in poor prognosis and worse outcomes. 18F-fluorodeoxyglucose (18F-FDG) PET/CT excels at visualizing inflammation but is suboptimal at detecting scar. We evaluated PET/CT sensitivity to detect scar and investigated the incremental diagnostic value of automated PET-derived data. METHODS: 176 patients who underwent cardiac magnetic resonance (CMR) and N-13 ammonia/18F-FDG cardiac PET/CT for suspected CS within 3 months were enrolled. Scar was defined as late gadolinium enhancement (LGE) on CMR without concordant 18F-FDG uptake on 18F-FDG PET/CT. Accuracy of cardiac PET/CT at detecting scar (perfusion defect without concordant 18F-FDG uptake) was assessed before and after addition of automated PET-derived data. RESULTS: Sensitivity of PET/CT for scar detection was 45.3% (specificity 88.9%). Addition of PET-derived LV volumes and function in a logistic regression model improved sensitivity to 57.0% (specificity: 80.0%, AUC 0.72). Addition of phase analysis maximum segmental onset of myocardial contraction > 61 improved AUC to 0.75, correctly relabeling 16.3% of patients as scar (net reclassification index 8.2%). CONCLUSION: Sensitivity of gated PET MPI alone for scar detection in CS is suboptimal. Adding PET-derived volumes/function and phase analysis data results in improved detection and characterization of scar.

An under-recognized phenomenon: Myocardial volume change during the cardiac cycle.

BACKGROUND: Myocardial volume is assumed to be constant over the cardiac cycle in the echocardiographic models used by professional guidelines, despite evidence that suggests otherwise. The aim of this paper is to use literature-derived myocardial strain values from healthy patients to determine if myocardial volume changes during the cardiac cycle. METHODS: A systematic review for studies with longitudinal, radial, and circumferential strain from echocardiography in healthy volunteers ultimately yielded 16 studies, corresponding to 2917 patients. Myocardial volume in systole (MVs) and diastole (MVd) was used to calculate MVs/MVd for each study by applying this published strain data to three models: the standard ellipsoid geometric model, a thin-apex geometric model, and a strain-volume ratio. RESULTS: MVs/MVd<1 in 14 of the 16 studies, when computed using these three models. A sensitivity analysis of the two geometric models was performed by varying the dimensions of the ellipsoid and calculating MVs/MVd. This demonstrated little variability in MVs/MVd, suggesting that strain values were the primary determinant of MVs/MVd rather than the geometric model used. Another sensitivity analysis using the 97.5th percentile of each orthogonal strain demonstrated that even with extreme values, in the largest two studies of healthy populations, the calculated MVs/MVd was <1. CONCLUSIONS: Healthy human myocardium appears to decrease in volume during systole. This is seen in MRI studies and is clinically relevant, but this study demonstrates that this characteristic was also present but unrecognized in the existing echocardiography literature.

Moving from volume to value for revascularization in stable ischemic heart disease: A review.

IMPORTANCE: Although percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are both commonly employed in the treatment of stable ischemic heart disease (SIHD), their ability to reduce subsequent heart attacks and death is currently in question. These procedures will come under increasing scrutiny as the healthcare reimbursement system moves away from the traditional fee for service model in favor of "pay for value". OBSERVATION: Both international and domestic data show wide variability in the use of PCI and CABG in patients with SIHD. There is evidence of ongoing quality improvement over the last 5 years in reducing the use of inappropriate procedures, but there is still room for improvement. We present ideas regarding health policy interventions that might help manage the transition to value-based payments in this area, including improvements in national registries, more rapid revision of appropriate use criteria, shared decision making, and evidence-based management of PCI in SIHD. CONCLUSIONS AND RELEVANCE: The use of revascularization procedures in patients with SIHD is potentially a model for how care might be improved with health care policy intervention. We suggest that the status quo, although apparently improved over the last 5 years, is still unacceptable when 25% of hospitals have a rate of unnecessary PCI in patients with SIHD that approaches 25%.

Use of echocardiography in outpatients with chest pain and normal resting electrocardiograms referred to Mayo Clinic Rochester.

OBJECTIVES: To determine how often unnecessary resting echocardiograms that are "not recommended" by clinical practice guidelines are performed in patients with stable chest pain and normal resting electrocardiograms (ECGs). BACKGROUND: There are scant data to indicate how often Class III recommendations are ignored in clinical practice. PATIENTS AND METHODS: We searched electronically all medical records of referral outpatients seen at Mayo Clinic Rochester from January 1, 2010, through December 31, 2013, to identify patients with stable chest pain and known or suspected coronary artery disease who underwent resting echocardiography and had normal resting ECGs and no other indication for echocardiography. RESULTS: Of the 15,529 referral outpatients who were evaluated at Mayo Clinic Rochester with chest pain, 3976 (25.6%) had resting echocardiograms. Eight hundred seventy of these 3976 patients (21.9%) had normal resting ECGs. Six hundred nineteen of these 870 patients (71.1%) had other indications for echocardiography. The remaining 251 patients (6.3% of all echocardiograms and 1.6% of all patients) had normal resting ECGs and no other indication for echocardiography. Two hundred thirty-nine of these 251 patients (95.2%) had normal echocardiograms. Of the 12 abnormal echocardiograms, only 4 led to any change in clinical management. Sixty-one of these 251 echocardiograms (24.3%) were "preordered" before the provider (physicians, nurses, physician assistants) visit. CONCLUSION: Echocardiograms were performed in 1 in 4 referral outpatients with chest pain seen at Mayo Clinic Rochester. However, only 1 in 16 of these echocardiograms was performed in violation of the class III recommendation in the American College of Cardiology Foundation/American Heart Association guidelines for the management of stable angina. These unnecessary echocardiograms were almost always normal, and had little impact on clinical management. The rate of unnecessary echocardiograms could be decreased by eliminating preordering.

Temporal trends of single-photon emission computed tomography myocardial perfusion imaging in patients without prior coronary artery disease: A 22-year experience at a tertiary academic medical center.

BACKGROUND: Between 1990 and 2006, there was a large national increase in utilization of single-photon emission computed tomography myocardial perfusion imaging (SPECT) for assessment of coronary artery disease (CAD). We aim to examine the trends of SPECT test results and patients' characteristics at Mayo Clinic Rochester. METHODS: Using the Mayo Clinic nuclear cardiology database, we examined all SPECT tests performed between January 1, 1991, and December 31, 2012, in patients without prior CAD. The study cohort was divided into 5 time periods: 1991-1995, 1996-2000, 2001-2005, 2006-2010, and 2011-2012. RESULTS: There were 35,894 eligible SPECT tests (mean age 62.5 ± 12 years, 54% men). Annual utilization of SPECT increased significantly in 1992-2002 but then decreased without evidence of test substitution with stress echocardiography. There were modest changes in CAD risk factors over time. Testing of asymptomatic patients doubled (21.9% in 1991-1995 to 40% in 2006-2010) but later decreased to 33.6% in 2011-2012. Tests on patients with typical angina decreased dramatically (18.3% in 1991-1995 to 6.7% in 2011-2012). Summed stress score, summed difference score, and high-risk SPECT tests all decreased over time in both symptomatic and asymptomatic patients regardless of stress modality (exercise vs pharmacologic). CONCLUSIONS: In Mayo Clinic Rochester, annual SPECT utilization in patients without prior CAD increased in 1992-2002 but then decreased. Despite similar CAD risk factors and decreased utilization after 2003, more tests were low risk; summed stress score, summed difference score, and high-risk tests all decreased. Our findings confirm previous observations that SPECT was increasingly used in patients with a lower prevalence of CAD.

Downstream clinical implications of abnormal myocardial perfusion single-photon emission computed tomography based on appropriate use criteria.

BACKGROUND: Appropriate use criteria (AUC) for single-photon emission computed tomography myocardial perfusion images (SPECT-MPI) were developed to address the growth of cardiac imaging studies. However, these criteria have not been vigorously validated. We sought to determine the rate of abnormal stress SPECT-MPI studies and subsequent revascularization procedures as categorized by AUC. METHODS: We retrospectively examined 280 patients who underwent stress SPECT-MPI and categorized these studies as appropriate, inappropriate, or uncertain based on AUC. Data regarding subsequent angiography and revascularization within 6 months after stress SPECT-MPI were collected from the electronic medical record. RESULTS: 280 patients met the inclusion criteria (mean age 67.3 ± 11.4 years, 36 % female). When categorized by AUC, 62.9 % (N = 176) of stress SPECT-MPI were considered appropriate, 13.6 % (N = 38) uncertain, and 23.6 % (N = 66) inappropriate. Appropriate stress SPECT-MPI studies were more likely to have intermediate or high risk results than uncertain or inappropriate studies [40 % (N = 71) vs. 21 % (N = 8) and 18 % (N = 12), respectively; P = 0.008)]. Appropriate studies were associated with an increased rate of coronary angiography [14 % (N = 25)] compared to the uncertain (0 %) and inappropriate [3 % (N = 2)] studies (P = 0.003). There was also an increased rate of revascularization after appropriate studies [9 % (N = 16)] compared to the uncertain (0 %) and inappropriate (0 %) studies (P = 0.006). CONCLUSIONS: Appropriate stress SPECT-MPI studies are more likely to result in abnormal results requiring subsequent revascularization compared to inappropriate and uncertain stress studies. Inappropriate and uncertain stress SPECT-MPI did not lead to subsequent revascularization.

Appropriate use criteria for stress single-photon emission computed tomography sestamibi studies: a quality improvement project.

BACKGROUND: We previously reported the application of the 2005 American College of Cardiology Foundation appropriate use criteria for stress single-photon emission computed tomography (SPECT) imaging to patients at Mayo Clinic (Rochester, MN) in 2005 and 2006. A subsequent internal quality improvement project focused on physician education in an attempt to reduce the rate of inappropriate SPECT studies. METHODS AND RESULTS: Our 2008 physician education effort, focused on 4 specific indications that accounted for 88% of the inappropriate SPECT studies, included a presentation at medical grand rounds, a publication in the staff newsletter, meetings with physician administrators, and focused presentations to departments/divisions with many ordering physicians. We then remeasured the appropriateness of SPECT studies using previously published methods. The general categories of study indications, eg, after revascularization, were similar in 273 SPECT patients in 2008 and in our 2005 (n=284) and 2006 (n=284) cohorts. There was a trend suggesting a change in the overall classification of appropriateness over time (P=0.08) and a significant change in the rate of inappropriate studies over time (P=0.018). Inappropriate studies decreased from 14.4% in 2005 to 7.0% in 2006 before initiation of the quality improvement project. After completion of the quality improvement project, inappropriate studies increased to 11.7% (P=0.06). The 95% confidence limits for the 4.7% increase in inappropriate studies after the quality improvement project included a decrease of 0.2% and an increase of 9.6%. CONCLUSIONS: This quality improvement project, focused on feedback, physician education, and remeasurement, did not reduce the rate of inappropriate stress SPECT studies in a single academic medical center. Similar limited interventions focused on physician education alone may have limited benefit. More extensive intervention may be necessary to improve the quality of care with appropriateness criteria.

Comparative effectiveness of exercise electrocardiography with or without myocardial perfusion single photon emission computed tomography in women with suspected coronary artery disease: results from the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) trial.

BACKGROUND: There is a paucity of randomized trials regarding diagnostic testing in women with suspected coronary artery disease (CAD). It remains unclear whether the addition of myocardial perfusion imaging (MPI) to the standard ECG exercise treadmill test (ETT) provides incremental information to improve clinical decision making in women with suspected CAD. METHODS AND RESULTS: We randomized symptomatic women with suspected CAD, an interpretable ECG, and ≥5 metabolic equivalents on the Duke Activity Status Index to 1 of 2 diagnostic strategies: ETT or exercise MPI. The primary end point was 2-year incidence of major adverse cardiac events, defined as CAD death or hospitalization for an acute coronary syndrome or heart failure. A total of 824 women were randomized to ETT or exercise MPI. For women randomized to ETT, ECG results were normal in 64%, indeterminate in 16%, and abnormal in 20%. By comparison, the exercise MPI results were normal in 91%, mildly abnormal in 3%, and moderate to severely abnormal in 6%. At 2 years, there was no difference in major adverse cardiac events (98.0% for ETT and 97.7% for MPI; P=0.59). Compared with ETT, index testing costs were higher for exercise MPI (P<0.001), whereas downstream procedural costs were slightly lower (P=0.0008). Overall, the cumulative diagnostic cost savings was 48% for ETT compared with exercise MPI (P<0.001). CONCLUSIONS: In low-risk, exercising women, a diagnostic strategy that uses ETT versus exercise MPI yields similar 2-year posttest outcomes while providing significant diagnostic cost savings. The ETT with selective follow-up testing should be considered as the initial diagnostic strategy in symptomatic women with suspected CAD. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00282711.

The impact of ordering provider specialty on appropriateness classification.

BACKGROUND: There is limited published data comparing the appropriateness use criteria for SPECT MPI with the specialty of the ordering provider. The aim of this study was to examine if the specialty of the ordering provider affected either the ordering indication or the appropriateness of stress SPECT MPI. METHODS AND RESULTS: The ordering provider's specialty was compared with the study indication and appropriateness rating. There were modest but significant differences in general indications by specialty. For example, the Emergency Department group ordered fewer studies in asymptomatic patients (3% compared to 14%-23% in the other four referral groups). In contrast, 43% of the studies ordered by Cardiovascular Division physicians and 39% of the studies ordered by the Registered Nurse group were on post-revascularization patients, compared to 23%-31% of those ordered by the other three groups. Overall appropriateness classification did not differ among the five specialty groups (P 5 0.19). CONCLUSION: In a clinical practice where pre-operative testing using SPECT is infrequent,the rate of inappropriate studies was similar for all ordering providers. Quality improvement efforts in similar practices will likely require a broad educational focus on all ordering providers.

Impact of left ventricular function and the extent of ischemia and scar by stress myocardial perfusion imaging on prognosis and therapeutic risk reduction in diabetic patients with coronary artery disease: results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

BACKGROUND: The Bypass Angioplasty Revascularization Investigation 2 Diabetes trial demonstrated similar long-term clinical effectiveness of revascularization (REV) and intensive medical (MED) therapy. Comparisons of post-intervention ischemic burden have not been explored but are relevant to treatment decisions. This study examined differences in 1-year stress myocardial perfusion SPECT (MPS) abnormalities by randomized treatment. METHODS: MPS was performed in 1,505 patients at 1-year following randomization. MPS images were analyzed (masked to treatment) by a Nuclear Core Laboratory using a quantitative percent (%) of total, ischemic, and scarred myocardium. Cox proportional hazards models were used to estimate the relationship between MPS variables and trial endpoints. RESULTS: At 1-year, nearly all REV patients underwent the assigned procedure; while 16% of those randomized to MED received coronary REV. Patients randomized to REV exhibited fewer stress perfusion abnormalities than MED patients (P < .001). CABG patients had more frequent ischemic and scarred myocardium encumbering ≥ 5% of the myocardium when compared to those receiving PCI. Patients randomized to MED had more extensive ischemia and the median % of the myocardium with perfusion abnormalities was lower following REV (3% vs 9%, P = .01). A total of 59% of REV patients had no inducible ischemia at 1-year compared to 49% of MED patients (P < .001). Within the CABG stratum, those randomized to MED had the greatest rate of ischemic (P = .032) and scarred (P = .017) perfusion abnormalities. At 1-year, more extensive and severe stress myocardial perfusion abnormalities were associated with higher 5-year rates of death and a combined endpoint of cardiac death or myocardial infarction (MI) rates (11.3%, 8.1%, 6.8%, for ≥ 10%, 5%-9.9%, and 1-4.9% abnormal myocardium at stress, respectively, P < .001). In adjusted models, selected MPS variables were significantly associated with an increased hazard of cardiac death or MI (hazard ratio = 1.11 per 5% increase in abnormal myocardium at stress, P = .004). CONCLUSIONS: Patient management strategies that focus on ischemia resolution can be useful to guide the efficacy of near-term therapeutic approaches. A 1-year post-therapeutic intervention myocardial perfusion scan provides important information regarding prognosis in stable CAD patients with diabetes.

Early image acquisition using a solid-state cardiac camera for fast myocardial perfusion imaging.

BACKGROUND: A novel ultra-fast solid-state cardiac camera (Discovery NM 530c, General Electric) allows much shorter acquisition times compared to standard dual-detector SPECT cameras. This design enables investigation of the potential for early myocardial perfusion imaging (MPI) following a rest injection of technetium-99m (Tc-99m) rather than the conventional 45-60 minute delay in image acquisition. METHODS: A total of 30 patients underwent MPI at rest using Tc-99m sestamibi (n = 9) or tetrofosmin (n = 21). A 12 minute image acquisition in list mode was performed immediately following isotope injection. Patients also underwent a conventional delayed image acquisition 60 minutes following the rest isotope injection (image acquisition over 4 minutes). The immediate 12 minute acquisition was divided into three 4-minute intervals for image reconstruction (0-4, 4-8, and 8-12 minutes). The perfusion images were interpreted by two experienced physicians who evaluated each study for overall image quality (good, acceptable, or unacceptable) and graded each image using the summed rest score (SRS) and the standard 17-segment, 5-point scale model. RESULTS: The images acquired in the 0-8 minute time interval were predominantly uninterpretable due to excessive blood pool uptake. The images acquired in the 8-12 minute time interval were interpretable and compared to the conventional images obtained at 60 minutes. Overall image quality was better on the 60 minute image (17 good, 13 acceptable) compared with 8-12 minute image (3 good, 25 acceptable, 2 unacceptable). Sixteen of the 30 patients had an improvement in overall image quality by at least one category using the 60 minute delayed image. Nine of the 30 patients (2 Tc-99m sestamibi; 7 Tc-99m tetrofosmin) had at least one uninterpretable myocardial segment due to liver and/or bowel overlapping the myocardium on the 8-12 minute images vs 1 patient (1 myocardial segment) with this problem on the 60 minute delayed images (P = .005). Uninterpretable segments (total of 16) on the 8-12 minute images were confined to the apex and inferior wall. The mean SRS of the interpretable 8-12 minute images (n = 21) was 3.2 (95% confidence intervals; 1.0, 5.4) compared to 1.6 (95% confidence intervals; 0, 3.3) on the 60 minute delayed images in those patients (P = .005). CONCLUSIONS: Overall image quality was better with fewer uninterpretable studies and a lower SRS on the rest images obtained at 60 minutes compared to early image acquisition (8-12 minutes following isotope injection). These findings do not support the routine use of early image acquisition with this new solid-state ultra-fast camera system.

Myocardial Ischemia in the Management of Chronic Coronary Artery Disease: Past and Present.

For many years, stress-induced myocardial ischemia has been considered important in the management of chronic coronary artery disease. Early evidence focused on the exercise ECG and the Duke treadmill score. In the 1970s, randomized clinical trials, which compared coronary artery bypass surgery to medical therapy, enrolled patients who were very different from contemporary practice and had inconsistent results. Surgery appeared to be of greatest benefit in high-risk patients defined by anatomy (such as left main disease) or stress-induced ischemia. However, randomized clinical trials of revascularization versus contemporary medical therapy over the past 20 years have been surprisingly negative. Nuclear cardiology substudies from these trials reported inconsistent results. Two observational studies from a single-center provided the best evidence for the use of stress-induced ischemia to identify patients who were most likely to benefit from revascularization. The recently completed ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) was designed to test the hypothesis that revascularization would improve outcomes in patients with moderate-severe ischemia on stress testing. Unfortunately, 14.2% of the randomized patients had either mild or no ischemia on core lab review. Nearly one-quarter of the patients were randomized on the basis of an exercise ECG without imaging. The negative results of the trial reflect the long-term population decline in coronary artery disease and abnormal stress tests, as well as improvements in patient outcome due to optimal medical therapy. Topics requiring further research are presented. The implications of the trial for the use of both stress imaging and coronary computed tomography angiography in clinical practice are examined.

Cardiac MRI demonstrates compressibility in healthy myocardium but not in myocardium with reduced ejection fraction.

BACKGROUND: The professional guidelines assume that the myocardial volume in systole (MVs) is equal to that in diastole (MVd), despite some limited evidence that points to the contrary. The aim of this manuscript is to determine whether this is true in healthy myocardium using gold standard cardiac MRI, as well as transthoracic echocardiography (TTE). The secondary aim is to determine whether there are similar MV changes in patients with heart failure with reduced ejection fraction (HFrEF). METHOD: A prospectively derived cohort at Mayo Clinic of 115 adult subjects (mean age 42.8 years, 58% female) with no cardiac risk factors was identified. Cardiac MRI was obtained on all 115 patients, 51 of whom also consented to a TTE. MRI from a retrospectively derived cohort of 50 HFrEF patients was also collected. MVs and MVd was calculated using standard approaches with inclusion of the papillary muscles. RESULTS: In the healthy population, MRI demonstrated MVs/MVd = 0.87 (SD 0.04) and TTE demonstrated MVs/MVd = 0.79 (SD 0.07), suggesting compressibility (p < 0.0001). In the 51 healthy patients who received both imaging modalities, MVs/MVd was 8.0% higher in MRI than TTE (p < 0.0001), but both modalities had MVs/MVd < 1 (p < 0.0001). A Bland-Altman plot demonstrated that as the mean MVs/MVd increases, the difference in MVs/MVd MRI-TTE declines (r = -0.53, p < 0.0001). However, in HFrEF populations, MVs/MVd = 1.01 (0.03), suggesting myocardial incompressibility. CONCLUSION: Contrary to currently accepted standards, healthy myocardium is compressible but HFrEF myocardium is incompressible. The ratio MVs/MVd merits further study in an expanded normal cohort and in disease states.