The "fixed" SPECT MPI defect: Where are we and where should we be going?

This brief review focuses on reasons why myocardial perfusion imaging (MPI) SPECT defects may appear "fixed" (rest vs stress). A combination of technical and physiology factors are responsible in most cases and are discussed. Perhaps the major reason defects will appear fixed is that there is no absolute quantitative measurement of myocardial blood flow (MBF, rest and stress) with which to assess the magnitude and potential direction of change in the defect vs reference zone with stress. Cardiac PET MPI provides absolute measurements of MBF required to understand the clinical significance of the SPECT "fixed" defect and are highlighted. Emphasis is given to use of the actual MBF measurements though indexing stress MBF to that of truly normal subjects (RFR or FFRPET) will prove useful in recognition of multi-vessel CAD. The availability of 18F flurpiridaz for clinical use is likely to encourage more widespread adoption of cardiac PET MPI for evaluation of patients with known or suspected CAD.

Myocardial Viability: Survival Mechanisms and Molecular Imaging Targets in Acute and Chronic Ischemia.

Myocardial responses to acute ischemia/reperfusion and to chronic ischemic conditions have been studied extensively at all levels of organization. These include subcellular (eg, mitochondria in vitro); intact, large animal models (eg, swine with chronic coronary stenosis); as well as human subjects. Investigations in humans have used positron emission tomographic metabolic and myocardial blood flow measurements, assessment of gene expression and anatomic description of myocardium obtained at the time of coronary artery revascularization, ventricular assist device placement, or heart transplantation. A multitude of genetic, molecular, and metabolic pathways have been identified, which may promote either myocyte survival or death or, most interestingly, both. Many of these potential mediators in both acute ischemia/reperfusion and adaptations to chronic ischemic conditions involve the mitochondria, which play a central role in cellular energy production and homeostasis. The present review is focused on operative survival mechanisms and potential myocardial viability molecular imaging targets in acute and chronic ischemia, especially those which impact mitochondrial function.

Coronary circulation: Pressure/flow parameters for assessment of ischemic heart disease.

Both invasive and non-invasive parameters have been reported for assessment of the physiological status of the coronary circulation. Fractional flow reserve and coronary (or myocardial) flow reserve may be obtained by invasive or non-invasive means. These metrics of coronary stenosis severity have achieved wide clinical acceptance for guiding revascularization decisions and risk stratification. Other indices are obtained invasively (e.g., instantaneous wave-free ratio, iFR; hyperemic stenosis resistance) or non-invasively (e.g., PET absolute myocardial blood flow (mL/min/g)) and have been used for the same purposes. Both iFR, and whole-cycle distal coronary to aortic mean pressure (Pd/Pa) are measured under basal condition and used for assessment of hemodynamic stenosis severity as is index of basal stenosis resistance (BSR). These metrics typically are dichotomized at an empirically derived cut point into "normal" and "abnormal" categories for purposes of clinical decision making and data analysis. Once dichotomized the indices do not always point in the same direction and so confusion may arise. This review, therefore, will present basic principles relevant to understanding commonly employed metrics of the physiological status of the coronary circulation, potential strengths and weaknesses, and hopefully an improved appreciation of the clinical information provided by each.

Utilization of stress testing for low-risk patients with chest discomfort in the emergency department.

BACKGROUND: The management of patients presenting to an emergency department with chest discomfort at low-risk for acute coronary syndrome represents a common clinical challenge. Such patients are often triaged to chest pain units for monitoring and cardiac stress testing for further risk stratification. METHODS: We conducted a retrospective study of 292 low-risk patients who presented to an emergency department with chest discomfort. We performed physician-adjudicated chart reviews of all patients with positive stress tests to assess downstream testing, subsequent coronary revascularization, and outcomes. RESULTS: Of the 292 patients, 33 (11.3%) had stress tests positive for ischemia, and 12 (4.1%) underwent diagnostic cardiac catheterization. Of the 292 patients, 4 (1.4%) underwent coronary revascularization that may have resulted in a mortality benefit. CONCLUSION: These data suggest a very low yield of detecting clinically significant coronary disease with stress testing low-risk patients with chest discomfort in emergency department chest pain units.

Reinnervation post-heart transplantation.

Heart transplantation results in complete denervation of the donor heart with loss of afferent and efferent nerve connections. The majority of patients remain completely denervated during the first 6-12 months following transplantation. Evidence of reinnervation is usually found during the second year after transplantation and involve the myocardial muscle, sinoatrial node, and coronary vessels, but remains incomplete and regionally limited many years post-transplant. Restoration of cardiac innervation can improve exercise capacity as well as blood flow regulation in the coronary arteries, and hence improve quality of life. As yet, there is no evidence that the reinnervation process is associated with the occurrence of allograft-related events or survival.

Correction to: Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC.

The above position statement originally published containing errors in the author metadata; specifically, the Expert Content Reviewers-Andrew Einstein, Raymond Russell and James R. Corbett-were tagged as full authors of the paper. The article metadata has now been corrected to remove Drs. Einstein, Russell and Corbett from the author line, and the PubMed record has been updated accordingly.

Integration of Quantitative Positron Emission Tomography Absolute Myocardial Blood Flow Measurements in the Clinical Management of Coronary Artery Disease.

In the >40 years since planar myocardial imaging with(43)K-potassium was introduced into clinical research and management of patients with coronary artery disease (CAD), diagnosis and treatment have undergone profound scientific and technological changes. One such innovation is the current state-of-the-art hardware and software for positron emission tomography myocardial perfusion imaging, which has advanced it from a strictly research-oriented modality to a clinically valuable tool. This review traces the evolving role of quantitative positron emission tomography measurements of myocardial blood flow in the evaluation and management of patients with CAD. It presents methodology, currently or soon to be available, that offers a paradigm shift in CAD management. Heretofore, radionuclide myocardial perfusion imaging has been primarily qualitative or at best semiquantitative in nature, assessing regional perfusion in relative terms. Thus, unlike so many facets of modern cardiovascular practice and CAD management, which depend, for example, on absolute values of key parameters such as arterial and left ventricular pressures, serum lipoprotein, and other biomarker levels, the absolute levels of rest and maximal myocardial blood flow have yet to be incorporated into routine clinical practice even in most positron emission tomography centers where the potential to do so exists. Accordingly, this review focuses on potential value added for improving clinical CAD practice by measuring the absolute level of rest and maximal myocardial blood flow. Physiological principles and imaging fundamentals necessary to understand how positron emission tomography makes robust, quantitative measurements of myocardial blood flow possible are highlighted.

PET measurements of myocardial blood flow post myocardial infarction: Relationship to invasive and cardiac magnetic resonance studies and potential clinical applications.

This review focuses on clinical studies concerning assessment of coronary microvascular and conduit vessel function primarily in the context of acute and sub acute myocardial infarction (MI). The ability of quantitative PET measurements of myocardial blood flow (MBF) to delineate underlying pathophysiology and assist in clinical decision making in this setting is discussed. Likewise, considered are physiological metrics fractional flow reserve, coronary flow reserve, index of microvascular resistance (FFR, CFR, IMR) obtained from invasive studies performed in the cardiac catheterization laboratory, typically at the time of PCI for MI. The role both of invasive studies and cardiac magnetic resonance (CMR) imaging in assessing microvascular function, a key determinant of prognosis, is reviewed. The interface between quantitative PET MBF measurements and underlying pathophysiology, as demonstrated both by invasive and CMR methodology, is discussed in the context of optimal interpretation of the quantitative PET MBF exam and its potential clinical applications.

Functional Versus Anatomic Imaging of CAD: Lessons Learned from Recent Clinical Trials.

Recent clinical trials directed at imaging of coronary artery disease (CAD) have demonstrated a paradigm shift away from endpoints related to detection of CAD in favor of those related to clinical outcomes. The objective of such trials has been to determine whether physiological metrics are superior to anatomical ones for guiding therapy and improving outcomes in patients with known or suspected CAD. The present review focuses on selected trials in this area in particular DEFER, FAME 1 and 2, a meta-analysis comparing FFR to anatomically guided treatment outcomes and COURAGE SPECT MPI sub study. The rationale for using physiological as opposed to anatomical endpoints to optimize patient management, in particular coronary revascularization decisions, is emphasized. The results of the FFR-based trials are concordant and indicate physiological metrics are superior to anatomical ones for guiding therapy and improving clinical outcomes in patients with known or suspected CAD.

Impact of myocardial viability and left ventricular lead location on clinical outcome in cardiac resynchronization therapy recipients with ischemic cardiomyopathy.

INTRODUCTION: Cardiac resynchronization therapy (CRT) recipients with ischemic cardiomyopathy (ICM) have scar segments that may limit ventricular resynchronization and clinical response. The impact of myocardial viability at the left ventricular (LV) pacing site on CRT response is poorly elucidated. METHODS AND RESULTS: A retrospective cohort of 160 ICM patients with single photon emission computed tomography-myocardial perfusion imaging before device implantation were included. Coronary venous angiography and chest radiographs helped classify segmental location of LV lead (LVL). The primary outcome was a composite of heart failure (HF) hospitalization and mortality at 3 years, and secondary outcome was change in systolic function at 6 months. The patients were divided into groups based on the myocardial substrate at the site of LVL: LVL on or adjacent to (1) normal myocardium (LVL-N, n = 64), (2) segmental scar (LVL-S, n = 62), and (3) scar and ischemia (LVL-SI, n = 34). Upon follow-up, 75 (47%) patients reached primary endpoint with a higher incidence noted in LVL-S (60%), and LVL-SI (53%), compared to 31% in LVL-N (P = 0.004). Kaplan Meier method demonstrated poor event free survival for primary outcome in LVL-S (P = 0.002), and LVL-SI (P = 0.03). In Cox proportional hazard model, LVL-S (HR: 2.26, P = 0.004), and LVL-SI (1.9, P = 0.047) were independent predictors of primary outcome. CONCLUSION: In CRT recipients with ICM, scar and reversible ischemia in or adjacent to LV pacing site were independent predictors of HF hospitalization and death.

Cardiac PET-CT for monitoring medical and interventional therapy in patients with CAD: PET alone versus hybrid PET-CT?

This review focuses on optimal use of PET and PET-CT in monitoring medical and interventional therapy in patients with CAD. PET provides quantitative measurement of absolute myocardial blood flow and thus permits comprehensive physiological assessment of the coronary circulation. Hybrid PET-CT, in particular CCTA, adds anatomical information to maximal MBF measurement and so facilitates distinction of triple vessel focal epicardial disease from coronary microvascular disease or diffuse coronary atherosclerosis without focal stenoses. Hybrid PET-CT also may be of value in determining appropriateness and feasibility of percutaneous interventional therapy for chronic total coronary occlusion. PET alone, however, is the preferred modality to address functional status of the coronary circulation and response over time, if required, to medical or interventional therapy. CT at a minimum provides attenuation correction. More detailed CCTA should be added only when a well-defined need for anatomical information is required to answer the clinical question posed.

Myocardial Perfusion PET for the Detection and Reporting of Coronary Microvascular Dysfunction: A JACC: Cardiovascular Imaging Expert Panel Statement.

Angina pectoris and dyspnea in patients with normal or nonobstructive coronary vessels remains a diagnostic challenge. Invasive coronary angiography may identify up to 60% of patients with nonobstructive coronary artery disease (CAD), of whom nearly two-thirds may, in fact, have coronary microvascular dysfunction (CMD) that may account for their symptoms. Positron emission tomography (PET) determined absolute quantitative myocardial blood flow (MBF) at rest and during hyperemic vasodilation with subsequent derivation of myocardial flow reserve (MFR) affords the noninvasive detection and delineation of CMD. Individualized or intensified medical therapies with nitrates, calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1-receptor blockers, beta-blockers, ivabradine, or ranolazine may improve symptoms, quality of life, and outcome in these patients. Standardized diagnosis and reporting criteria for ischemic symptoms caused by CMD are critical for optimized and individualized treatment decisions in such patients. In this respect, it was proposed by the cardiovascular council leadership of the Society of Nuclear Medicine and Molecular Imaging to convene thoughtful leaders from around the world to serve as an independent expert panel to develop standardized diagnosis, nomenclature and nosology, and cardiac PET reporting criteria for CMD. This consensus document aims to provide an overview of the pathophysiology and clinical evidence of CMD, its invasive and noninvasive assessment, standardization of PET-determined MBFs and MFR into "classical" (predominantly related to hyperemic MBFs) and "endogen" (predominantly related to resting MBF) normal coronary microvascular function or CMD that may be critical for diagnosis of microvascular angina, subsequent patient care, and outcome of clinical CMD trials.

PET measurement of adenosine stimulated absolute myocardial blood flow for physiological assessment of the coronary circulation.

Considerable awareness has been raised of late of the need to reduce radiation exposure and control costs of x-ray and radionuclide imaging procedures. PET/CT cameras are now widely available and in conjunction with appropriate radionuclides and commercially available software make quantitative measurement of absolute MBF feasible for routine clinical practice. Quantitative measurement of absolute MBF under condition of coronary vasodilation permits independent assessment of the functional status of each of the three major coronary perfusion zones and so obviates the need for rest MBF determination in the great majority of cases. Coronary microvascular function also may be assessed in this same way. Thus, the stress-only protocol with quantitative PET measurement of MBF provides essential information required for clinical decision making related to need for catheterization and intervention for patients with known or suspected ischemic heart disease. Moreover, the single PET determination of maximal MBF in contrast to the usual rest/stress procedure addresses both safety and cost concerns. The present review focuses on: (1) quantitative PET measurements of myocardial blood flow for physiological assessment of the coronary circulation and (2) the value and potential limitations of performing stress only imaging in the clinical context.

Cardiac Imaging for Coronary Heart Disease Risk Stratification in Chronic Kidney Disease.

Chronic kidney disease (CKD), defined as dysfunction of the glomerular filtration apparatus, is an independent risk factor for the development of coronary artery disease (CAD). Patients with CKD are at a substantially higher risk of cardiovascular mortality compared with the age- and sex-adjusted general population with normal kidney function. The risk of CAD and mortality in patients with CKD is correlated with the degree of renal dysfunction including presence of microalbuminuria. A greater cardiovascular risk, albeit lower than for patients receiving dialysis, persists even after kidney transplantation. Congestive heart failure, commonly caused by CAD, also accounts for a significant portion of the cardiovascular-related events observed in CKD. The optimal strategy for the evaluation of CAD in patients with CKD, particularly before renal transplantation, remains a topic of contention spanning over several decades. Although the evaluation of coexisting cardiac disease in patients with CKD is desirable, severe renal dysfunction limits the use of radiographic and magnetic resonance contrast agents due to concerns regarding contrast-induced nephropathy and nephrogenic systemic sclerosis, respectively. In addition, many patients with CKD have extensive and premature (often medial) calcification disproportionate to the severity of obstructive CAD, thereby limiting the diagnostic value of computed tomography angiography. As such, echocardiography, non-contrast-enhanced magnetic resonance, nuclear myocardial perfusion, and metabolic imaging offer a variety of approaches to assess obstructive CAD and cardiomyopathy of advanced CKD without the need for nephrotoxic contrast agents.

Direct comparison of rest and adenosine stress myocardial perfusion CT with rest and stress SPECT.

INTRODUCTION: We have recently described a technique for assessing myocardial perfusion using adenosine-mediated stress imaging (CTP) with dual source computed tomography. SPECT myocardial perfusion imaging (SPECT-MPI) is a widely utilized and extensively validated method for assessing myocardial perfusion. The aim of this study was to determine the level of agreement between CTP and SPECT-MPI at rest and under stress on a per-segment, per-vessel, and per-patient basis. METHODS: Forty-seven consecutive patients underwent CTP and SPECT-MPI. Perfusion images were interpreted using the 17 segment AHA model and were scored on a 0 (normal) to 3 (abnormal) scale. Summed rest and stress scores were calculated for each vascular territory and patient by adding corresponding segmental scores. RESULTS: On a per-segment basis (n = 799), CTP and SPECT-MPI demonstrated excellent correlation: Goodman-Kruskall gamma = .59 (P < .0001) for stress and .75 (P < .0001) for rest. On a per-vessel basis (n = 141), CTP and SPECT-MPI summed scores demonstrated good correlation: Pearson r = .56 (P < .0001) for stress and .66 (P < .0001) for rest. On a per-patient basis (n = 47), CTP and SPECT-MPI demonstrated good correlation: Pearson r = .60 (P < .0001) for stress and .76 (P < .0001) for rest. CONCLUSIONS: CTP compares favorably with SPECT-MPI for detection, extent, and severity of myocardial perfusion defects at rest and stress.