Cold Pressor Testing and Sympathetic Nervous System Contribution to Ischemia with No Obstructive Coronary Artery Disease: Results from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Project.

Study Objective: Cold Pressor Testing (CPT) is a known stimulus of the sympathetic nervous system (SNS). To better understand sympathetic contribution to coronary blood flow regulation in women with suspected ischemia and no obstructive coronary arteries (INOCA), we compared myocardial perfusion reserve during CPT stress cardiac magnetic resonance (CMR) imaging between women with suspected INOCA and reference subjects. Design: Prospective cohort. Setting: Academic hospital. Participants: 107 women with suspected INOCA and 21-age-matched reference women. Interventions: CPT stress CMR was performed with measurement of myocardial perfusion reserve index (MPRI), adjusted for rate pressure product (MPRIRPP). Invasive coronary function testing in a subset of INOCA women (n=42) evaluated for endothelial dysfunction in response to acetylcholine, including impaired coronary diameter response ≤0% and coronary blood flow response (ΔCBF) <50%. Main Outcome Measure: MPRIRPP. Results: Compared to reference women, the INOCA group demonstrated higher resting RPP (p=0.005) and CPT MPRIRPP (1.09±0.36 vs 0.83±0.18, p=0.002). Furthermore, INOCA women with impaired ΔCBF (n=23) had higher CPT MPRIRPP (p=0.044) compared to reference women despite lower left ventricular ejection fraction (64±7 % vs 69±2 %, p=0.005) and mass-to-volume ratio (0.79±0.15 vs 0.62±0.09, p<0.0001). These differences in CPT MPRIRPP did not persist after adjusting for age, body mass index, and history of hypertension. CPT MPRIRPP among INOCA women did not differ based on defined acetylcholine responses. Conclusions: Myocardial perfusion reserve to CPT stress is greater among women with INOCA compared to reference subjects. CPT induced a higher MPRIRPP also in women with coronary endothelial dysfunction, suggesting a greater contribution of the SNS to coronary flow than endothelial dysfunction. Further investigation in a larger cohort is needed.

Coronary computed tomography angiography for the evaluation of patients with acute chest pain.

Acute chest pain is a common presenting complaint of patients attending emergency room departments. Despite this, it can often be challenging to completely exclude a diagnosis of acute coronary syndrome following an initial standard clinical and biochemical evaluation. As a result of this, patients are often admitted to hospital until the treating clinician is satisfied that this diagnosis can be excluded. This process imparts a significant health economic burden by not only increasing hospital bed occupancy rates but also by the unnecessary layering of diagnostic investigations. With the rapid advances in coronary computed tomography angiography (CTA), there has been considerable interest in whether coronary CTA may be a viable alternative to this current standard care. We review the current literature and supporting evidence for utilising coronary CTA in the evaluation of patients presenting with acute chest pain in terms of its diagnostic accuracy, safety, cost-effectiveness and prognostic implications.

SPECT/PET myocardial perfusion imaging versus coronary CT angiography in patients with known or suspected CAD.

Stress SPECT myocardial perfusion imaging (MPI) is the most commonly utilized stress imaging technique for patients with suspected or known coronary artery disease (CAD) and has a robust evidence base including the support of numerous clinical guidelines. Gated SPECT is a well-established noninvasive imaging modalities that is a core element in evaluation of patients with both acute and stable chest pain syndromes. Over the past decade, PET has become increasingly used for the same applications. By comparison, cardiac computed tomography (CT) is a more recently developed method, providing non-invasive approaches for imaging coronary atherosclerosis and coronary artery stenosis. Non-contrast CT for imaging the extent of coronary artery calcification (CAC), in clinical use since the mid-1990's, has a very extensive evidence base supporting its use in CAD prevention. While contrast-enhanced CT for noninvasive CT coronary angiography (CCTA) is relatively new, it has already developed an extensive base of evidence regarding diagnosing obstructive CAD and more recently evidence has emerged regarding its prognostic value. It is likely that non-contrast CT or CCTA for assessment of extent of atherosclerosis will become an increasing part of mainstream cardiovascular imaging practices as a first line test. In some patients, further ischemia testing with MPI will be required. Similarly, MPI will continue to be widely used as a first-line test, and in some patients, further anatomic definition of atherosclerosis with CT will also be appropriate. This review will provide a synopsis of the available literature on imaging that integrates both CT and MPI in strategies for the assessment of asymptomatic patients for their atherosclerotic coronary disease burden and risk as well as symptomatic patients for diagnosis and guiding management. We propose possible strategies through which imaging might be used to identify asymptomatic candidates for more intensive prevention and risk factor modification strategies as well as symptomatic patients who would benefit from referral to invasive coronary angiography for consideration of revascularization.

Modern nuclear cardiac imaging in diagnosis and clinical management of patients with left ventricular dysfunction.

Congestive heart failure (CHF) has become a large social burden in modern Western society, with very high morbidity and mortality and extremely large financial costs. The largest cause of CHF is coronary heart disease, with ventricular dysfunction that may or may not be reversible by revascularization. Thus, evaluation of the viable myocardial tissue in patients with ischemic left ventricular (LV) dysfunction has important clinical and therapeutic implications. Furthermore, since patients with ventricular dysfunction are at higher operative risk, cardiologists and cardiac surgeons are commonly faced with issues regarding the balance between the potential risk vs benefit of revascularization procedures. Cardiac nuclear imaging [myocardial perfusion SPECT (MPS) and positron emission tomography (PET)] provide objective information that augments standard clinical and angiographic assessments of patients with ventricular dysfunction with respect to diagnosis (etiology), prognosis, and potential benefit from intervention. Development of the technology and methodology of gated MPS, now the routine method for MPS, allows assessment of the extent and severity of inducible ischemia as well as hypoperfused but viable myocardium, and also provides measurements of LV ejection fraction, regional wall motion, LV volume measurements, diastolic function and LV geometry. With PET, myocardial metabolism and blood flow reserve can be added to the measurements provided by nuclear cardiology procedures. This paper provides insight into the current evidence regarding settings in which nuclear cardiac imaging procedures are helpful in assessment of patients in the setting of coronary artery disease with severe LV dysfunction. A risk-benefit approach to MPS results is proposed, with principal focus on identifying patients at risk for major cardiac events who may benefit from myocardial revascularization.

Association of mitral annulus calcification, aortic valve sclerosis and aortic root calcification with abnormal myocardial perfusion single photon emission tomography in subjects age < or =65 years old.

OBJECTIVES: We examined the hypothesis that mitral annulus calcification (MAC), aortic valve sclerosis (AVS) and aortic root calcification (ARC) are associated with coronary artery disease (CAD) in subjects age < or =65 years. BACKGROUND: Mitral annulus calcification, AVS and ARC frequently coexist and are associated with coronary risk factors and CAD in the elderly. METHODS: We studied 338 subjects age < or =65 years who underwent evaluation of chest pain with myocardial perfusion single photon emission computed tomography (SPECT) and a two-dimensional transthoracic echocardiogram for other indications. The association of MAC, AVS and ARC with abnormal SPECT was evaluated by using chi-square analyses and logistic regression analyses. RESULTS: Compared with no or one calcium deposit and no or one coronary risk factor other than diabetes, multiple (> or =2) calcium (or sclerosis) deposits with diabetes or multiple (> or =2) coronary risk factors were significantly associated with abnormal SPECT in women age < or =55 years old (odds ratio [OR], 20.00), in women age >55 years old (OR, 10.00) and in men age < or =55 years old (OR, 5.55). Multivariate analyses identified multiple calcium deposits as a significant predictor for an abnormal SPECT in women (p < 0.001), younger subjects age < or =55 years (p < 0.05) and the total group of subjects (p < 0.01). CONCLUSIONS: When coronary risk factors are also taken into consideration, the presence of multiple calcium deposits in the mitral annulus, aortic valve or aortic root appears to be a marker of CAD in men < or =55 years old and women.

Quantitative analysis of regional motion and thickening by gated myocardial perfusion SPECT: normal heterogeneity and criteria for abnormality.

UNLABELLED: Quantitation of regional myocardial function is valuable in patients with coronary artery disease. This study assessed normal heterogeneity and developed and validated normal limits for quantitative regional motion and thickening by gated myocardial perfusion SPECT. METHODS: Patients underwent rest (201)Tl/exercise (99m)Tc-sestamibi gated SPECT. Reference values of motion and thickening for 20 myocardial segments were obtained in 105 patients with <5% likelihood of coronary disease (low-likelihood group). Criteria for abnormality of motion and thickening were defined for each segment, using receiver operator characteristic analysis, in 101 patients with coronary disease (training group). Semiquantitative visual interpretation was used as the gold standard. These criteria were prospectively validated in 100 patients (validation group). Criteria for grading motion and thickening abnormalities by severity levels were also defined and validated. RESULTS: Normal thickening decreased substantially along the longitudinal axis of the left ventricle, from 69% +/- 13% at the apex to 25% +/- 11% at the basal segments, whereas normal motion varied within the same ventricular plane. Validation of the criteria for abnormality yielded high accuracy in the detection of motion abnormalities (sensitivity, 88%; specificity, 92%) and thickening abnormalities (sensitivity, 87%; specificity, 89%). Quantitative motion and thickening segmental scores showed good agreement with visual scores. CONCLUSION: Normal regional myocardial contraction by gated myocardial perfusion SPECT is characterized by a substantial apex-to-base decline in thickening and by circumferential heterogeneity in endocardial motion. The assignment of segment-specific threshold values for defining motion and thickening abnormalities provided reasonably accurate identification and grading of regional myocardial dysfunction.

Evidence-based risk assessment in noninvasive imaging.

UNLABELLED: Assessment of important clinical and economic outcomes has become central to the evaluation of patient care. Outcome research is deeply rooted in epidemiology, including the use of multivariable, risk-adjusted regression analysis. In our current health care environment, these methods are increasingly being used to assess the quality of care and to profile physicians and laboratories. Nuclear medicine physicians therefore need to better understand outcome methodologies in order to evaluate patient outcomes, develop guidelines, and decide on patient management. METHODS: This review describes the methods of assessing the diagnostic and prognostic value of nuclear medicine techniques and, briefly, the methodologic limitations of sample size, frequency and type of events, and follow-up periods and the incremental value of imaging. Also described are logistic regression and Cox proportional hazards modeling. Models for risk assessment are designed to identify whether patients require conservative (i.e., low-risk) or aggressive (i.e., high-risk) treatment. Treatment selection is currently based on risk assessment and the formation of an integrated, empiric risk stratification algorithm of care. This review also includes the methods of assessing economic effectiveness and quality-of-life issues for patients examined with nuclear medicine techniques. CONCLUSION: In this era of constrained resources, low-cost outpatient-based care may be of increasing importance. High-quality evidence of the clinical and economic outcome of nuclear imaging is essential for helping health care providers and payers assess its value.

Serial changes on quantitative myocardial perfusion SPECT in patients undergoing revascularization or conservative therapy.

BACKGROUND: Little is known about changes of myocardial perfusion in patients undergoing coronary revascularization or medical therapy. The purpose of this observational study was to assess the long-term effects of revascularization or conservative therapy on serial quantitative myocardial perfusion single photon emission computed tomography (SPECT). METHODS AND RESULTS: The study population consisted of 421 patients who underwent serial rest thallium-201/stress technetium-99m sestamibi dual-isotope myocardial perfusion SPECT with at least a 1-year interval between the 2 studies and who had abnormal quantitative scan results on the first stress SPECT. The mean interval between scans was 32.7 +/- 15.9 months. Patients were divided into 3 groups according to stress defect extent: group 1 had small stress defects (4%-10%, n = 145), group 2 had intermediate stress defects (>10%-20%, n = 144), and group 3 had extensive stress defects (>20%, n = 132) at baseline. Forty patients in group 1, 44 in group 2, and 54 in group 3 underwent coronary revascularization between 2 SPECT studies; the others had conservative therapy. In group 3 patients with revascularization, stress defect extent and reversible defect extent were remarkably reduced (14.5% +/- 13.6% and 13.1% +/- 12.5%, respectively; both P <.0001), with greater improvement in those patients reporting increased use of cardiac medications; resting defect extent was slightly reduced (1.9% +/- 6.4%, P <.05). In group 3 patients with conservative therapy, a small reduction in stress defect extent was noted (2.3% +/- 8.3%, P <.05). In group 2, there were modest, similar reductions in reversible defect extent in both the patients with revascularization (2.7% +/- 7.7%, P <.05) and those with conservative therapy (1.8% +/- 7.3%, P <.05), as well as a small but significant reduction in stress defect extent in those with conservative therapy (2.1% +/- 8.2%, P <.05). In group 1 patients, no significant changes in stress, rest, or reversible defect extent were found with either therapy. CONCLUSIONS: The findings of this study show that improvement in quantitative myocardial perfusion abnormalities over time occurs in some patients with either revascularization or conservative therapy and suggest that, in patients with extensive defects, greater improvement may be seen in those who undergo revascularization.

Nuclear cardiology and electron-beam computed tomography: competitive or complementary?

Electron-beam computed tomography (EBCT) and nuclear cardiology techniques are both valuable in the noninvasive assessment of patients with suspected coronary artery disease. The techniques, however, are different in the information they provide about the patient. EBCT provides anatomic information on coronary atherosclerosis, whereas myocardial perfusion single-photon emission computed tomography assesses the physiologic significance of coronary stenosis. Because of these differences, the techniques are highly complementary. In considering the complementary nature of these methods, it is important to clarify the issues being raised. An important question in the consideration of a patient with known or suspected coronary artery disease is, What is the risk in an individual patient of developing clinical coronary artery disease? The answer to this question will determine who needs aggressive medical management. A second question in a suspected coronary artery disease patient is, What is the risk of cardiac death? As will be discussed, this risk, in general, determines the need to consider coronary revascularization. In the former question, EBCT testing and clinical assessment alone is usually sufficient, and in some cases nuclear testing can be of additional value. In answering the second question, on the basis of currently available data, the EBCT and nuclear cardiology studies appear to be operating in a complementary fashion.