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.

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.

Systolic-to-diastolic myocardial volume ratio as a novel imaging marker of cardiomyopathy.

BACKGROUND: In patients with normal left ventricular ejection fraction, it may be difficult to distinguish between the normal and diseased heart. Novel assessments of ventricular function, such as extracellular volume imaging, myocardial perfusion imaging and myocardial contraction fraction are emerging to better assess disease burden in these cases. This study endeavored to determine whether the ratio of myocardial volume in systole to myocardial volume in diastole (MVs/MVd), differs between normal hearts and those with disease states characterized by normal ejection fraction. METHOD: Consecutive patients from 2008 to 2018 with hypertrophic cardiomyopathy (HCM), cardiac amyloidosis, and heart failure with preserved ejection fraction (HFpEF) who underwent cardiac magnetic resonance imaging (MRI) were selected for inclusion, along with a sex- and age-matched cohort of normal volunteers who also underwent cardiac MRI. Manual tracings were performed on each MRI to calculate MVs/MVd, which was then compared across subgroups. RESULTS: Included were 50 patients with HCM, 50 patients with cardiac amyloidosis, 26 patients with HFpEF, and 30 normal subjects. Age was 54.1 years (SD 16.7); mean MVs/MVd was 0.88 (SD 0.04) in the normal subgroup, 1.03 (SD 0.06) in HCM patients, 1.03 (SD 0.06) in cardiac amyloidosis patients, and 0.97 (SD 0.02) in HFpEF patients, with all pathology subgroups different from the normal subgroup (p < .0001 for each). The ratio of MVs/MVd discriminated diseased from normal with c statistic 0.989 (p < .001). CONCLUSIONS: This study suggests that a novel and easily-captured metric of ventricular function, MVs/MVd, can differentiate normal ventricular function from multiple cardiomyopathies with normal ejection fractions.

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.

Coronary Disease Surveillance in the Community: Angiography and Revascularization.

Background Temporal declines in cardiac stress tests results, coronary revascularization, and cardiovascular mortality have suggested a decline in the population burden of coronary disease until the 2000s. However, recent data indicate these favorable trends could be ending. We aimed to assess the evolution of the population burden of coronary disease in the community by examining trends in angiography and revascularization. Methods and Results We analyzed age- and sex-adjusted trends from all coronary angiographic diagnostic procedures and revascularizations performed in Olmsted County, MN from 2000 to 2018. A total of 12 981 invasive angiograms were performed among 9049 individuals (64% men; 55% aged ≥65 years). Adjusted angiography rates decreased by 30% (95% CI, 25%-34%) between 2000 and 2009 and leveled off thereafter. Including computed tomography, angiography uncovered an increase in angiography use in recent years (risk ratio=1.15 [95% CI, 1.07-1.23] for 2018 versus 2014) and a decline in the prevalence of anatomic CAD from 2000 to 2018. CAD severity declined substantially from 2000 to 2009, followed by a plateau. Among 6570 revascularizations (72% men; 57% aged ≥65 years), 77% were percutaneous coronary interventions and 23% coronary artery bypass graft surgeries. The adjusted revascularization rates declined by 34% (95% CI, 27%-39%) from 2000 to 2009, followed by a plateau (risk ratio=1.10 [95% CI, 1.00-1.22]). Conclusions Between 2000 and 2018 in the community, coronary angiography use declined initially, leveled off, and then increased. Trends in CAD severity and revascularization use decreased then plateaued. The most recent trends are concerning as they suggest the burden of coronary disease is no longer declining. This warrants reinvigorated primary prevention and population surveillance.

Stress Testing in the Evaluation of Stable Chest Pain in a Community Population.

OBJECTIVE: To evaluate the use of stress testing in a community population with de novo stable chest pain, a normal resting electrocardiogram (ECG), and the ability to exercise. PATIENTS AND METHODS: We identified eligible patients by searching the electronic medical record of all outpatients seen at Mayo Clinic Rochester from January 1, 2010, through December 31, 2013. We determined the frequency of initial exercise stress testing, computed tomography coronary angiography, and invasive coronary angiography, as well as the use of subsequent second procedures (including percutaneous coronary intervention [PCI] and coronary artery bypass grafting) within 90 days. Patients were followed for 5 years for death, nonfatal myocardial infarction, and hospitalization for unstable angina. RESULTS: The data search identified 1175 patients with chest pain and normal resting ECGs. Only 331 patients underwent cardiac testing. A slight majority (185; 55.9%) underwent an exercise ECG alone. The remainder underwent exercise echocardiography (112; 33.8%), exercise single-photon-emission computed tomography (32; 9.7%), or computed tomography coronary angiography (2; 0.9%). Few patients (30; 9.1%) required additional testing within 90 days. Of the 14 patients (4.2%) who underwent invasive coronary angiography, 12 (85.7%) had significant coronary artery disease, and were referred for percutaneous coronary intervention or coronary artery bypass grafting. At 5 years, the mortality rate was 1.2%, and the combined event rate was 3.8%. CONCLUSION: Most community patients with chest pain and a normal resting ECG do not require further cardiac evaluation. In patients who require testing, and are able to exercise, noninvasive stress testing is preferred. Invasive coronary angiography is applied selectively and associated with a high rate of significant coronary artery disease and referral to coronary revascularization. Long-term outcomes are excellent.

Controversies in Diagnostic Imaging of Patients With Suspected Stable and Acute Chest Pain Syndromes.

There has been a tremendous growth quantity of high-quality imaging evidence in the area of acute and stable ischemic heart disease (SIHD). A number of recent comparative effectiveness trials have spurned significant controversies in the field of cardiovascular imaging. The result of this evidence is that many health care policies and national guidelines have undergone significant revisions. With all of this evidence, many challenges remain and the optimal evaluation strategy for evaluation of patients presenting with chest pain remains ill-defined. This paper enlisted the guidance of numerous experts in the field of cardiovascular imaging to garner their perspective on available imaging research in chest pain syndromes. Each of these vignettes represent editorial perspectives and diverse opinions as to which, if any, should be the primary test in the evaluation of stable chest pain. These perspectives are not meant to be all inclusive but to highlight many of the commonly discussed controversies in the evaluation of chest pain symptoms. These perspectives are presented as a pre-amble to an upcoming American College of Cardiology/American Heart Association clinical practice guideline that is undergoing revision from the previous report published in 2012. The evidence has changed considerably since the 2012 SIHD guideline, and the current perspectives represent the diversity of available evidence as to the optimal imaging strategy for evaluation of the symptomatic patient.

Phase analysis single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) detects dyssynchrony in myocardial scar and increases specificity of MPI.

BACKGROUND: Myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT) is commonly used to assess patients with cardiovascular disease. However, in certain scenarios, it may have limited specificity in the identification of hemodynamically significant coronary artery disease (e.g., false positive), potentially resulting in additional unnecessary testing and treatment. Phase analysis (PA) is an emerging, highly reproducible quantitative technology that can differentiate normal myocardial activation (synchrony) from myocardial scar (dyssynchrony). The objective of this study is to determine if PA can improve the specificity SPECT MPI. METHODS: An initial cohort of 340 patients (derivation cohort), referred for SPECT-MPI, was prospectively enrolled. Resting MPI studies were assessed for resting perfusion defects (scar). These were utilized as the reference standard for scar. Subsequently, we collected a second independent validation cohort of 138 patients and tested the potential of PA to reclassify patients for the diagnosis of "scar" or "no scar." Patients were assigned to three categories depending upon their pre-test probability of scar based on multiple clinical and imaging parameters: ≤ 10% (no scar), 11-74% (indeterminate), and ≥ 75% (scar). The ability of PA variables to reclassify patients with scar to a higher group and those without scar to a lower group was then determined using the net reclassification index (NRI). RESULTS: Entropy (≥ 59%) was independently associated with scar in both patient cohorts with an odds ratio greater than five. Furthermore, when added to multiple clinical/imaging variables, the use of entropy significantly improved the area under the curve for assessment of scar (0.67 vs. 0.59, p = 0.04). The use of entropy correctly reclassified 24% of patients without scar, by clinical model, to a lower risk category (as determined by pre-test probability) with an overall NRI of 18% in this validation cohort. DISCUSSION: The use of PA entropy can improve the specificity of SPECT MPI and may serve as a useful adjunctive tool to the interpreting physician. The current study determined the optimal PA parameters to detect scar (derivation cohort) and applied these parameters to a second, independent, patient group and noted that entropy (≥ 59%) was independently associated with scar in both patient cohorts. Therefore, PA, which requires no additional imaging time or radiation, enhances the diagnostic capabilities of SPECT MPI. CONCLUSION: The use of PA entropy significantly improved the specificity of SPECT MPI and could influence the labeling of a patient as having or not having myocardial scar and thereby may influence not only diagnostic reporting but also potentially prognostic determination and therapeutic decision-making.

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%.