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A condition of myocardium hibernation, typified by a steady-state decline in myocardial O2 consumption (MVO2) in connection with prolonged dilator capacity, results from chronic decrease of perfusion pressure and flow. Physiological responses may be the result of biochemical and morphological changes taking place in microvessel walls. Atrophy was dominant in walls of bigger microvessels and mild hypertrophy to the walls was evident for smaller microvessels.

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. • CKD is associated with increased risk of CAD, and the risk increases with worsening renal function. • Risks of revascularization are increased in patients with CKD, and long-term results are less favorable than those with normal renal function. • Diagnostic imaging studies should be directed toward patients with CKD whose risk of cardiac events is heightened and who are most likely to benefit from revascularization. • There are no compelling reasons to routinely select one particular stress imaging modality in preference to others, although there may be specific circumstances that favor a particular test. • Imaging techniques that require the use of contrast media that can cause contrast-induced nephropathy or nephrogenic systemic sclerosis should be avoided. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims We sought to compare the complementary prognostic value of exercise treadmill testing (ETT) and coronary computed tomographic angiography (CTA) among patients referred for both exams. Methods and results We studied 582 patients without known coronary artery disease (CAD) who were clinically referred for ETT and CTA within 6 months. Patientswere followed for cardiovascular (CV) death, non-fatal myocardial infarction (MI), or late revascularization (.90 days), stratified by Duke Treadmill Score (DTS) and CAD severity (≥50% stenosis). Mean age was 54+13 years (63% male). In median follow-up of 40 months, therewere 3 CV deaths, 7 non-fatal MIs, and 26 late revascularizations. ETTwas inconclusive in 23%, positive in 31%, and negative in 46%.CTAdemonstrated noCADin 37%, nonobstructive CADin 28%, and obstructive CADin 35%. Among low-risk ETT patients (n ¼ 326), therewere 3 MI, 10 late revascularizations, and the frequent presence of non-obstructive (32%, n ¼ 105) and obstructive CAD (27%, n ¼ 88). When present, ETT features (i.e. angina, DTS, ischaemic electrocardiogram changes, and exercise capacity) individually failed to predict CV death/MI after adjustment for Morise score. Conversely, both obstructive CAD [HR 4.9 (1.0-23.3), P ¼ 0.048] and CAD extent by segment involvement score .4 [HR 3.9 (1.0-15.2), P ¼ 0.049] predicted increased risk for CV death or MI. Conclusion Patients with a low-risk ETT have an excellent prognosis at 40 months, despite the frequent presence of non-obstructive (32%) and obstructive (27%) CAD. In patients with an intermediate- to high-risk ETT (DTS ,5), CTA can provide incremental risk stratification for future CV events. [ABSTRACT FROM AUTHOR]

The present paper reviews important recent publications concerning the application of principles of coronary physiology to quantitative PET myocardial perfusion imaging. Invasive measurements as well as coronary computed tomography angiography are also considered. The review focuses on physiological concepts relevant to the understanding of the effects of coronary atherosclerosis on myocardial blood flow (MBF) responses to stress. It also highlights the increasing shift from an anatomical paradigm of stenosis severity assessment to a physiological one, emphasizing the importance of absolute measurements of MBF. Key concepts and supporting literature reviewed in the present paper include quantitative PET measurements of absolute rest and stress MBF, the use of stress MBF alone for physiological assessment of stenosis functional severity, the utility of ratios such as fractional flow reserve (FFR) and coronary flow reserve (CFR) in assessing stenosis severity, and most importantly, the absolute level of MBF required to sustain vigorous physical exercise (9-10 metabolic equivalents (METs)) in healthy adults. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Left main disease (LMD) and three-vessel disease (3VD) have important prognostic value in patients with coronary artery disease. However, uncertainties still exist about their prevalence and predictors in patients with acute coronary syndrome (ACS) and also in patients with stable coronary disease. Thus the aim of this study was to perform an international collaborative systematic review and metaanalysis to appraise the prevalence and predictors of LMD and 3VD. Methods Medline/PubMed were systematically searched for eligible studies published up to 2010, reporting multivariate predictors of LMD or 3VD. Study features, patient characteristics, and prevalence and predictors of LMD and 3VD were abstracted and pooled with random-effect methods (95% CIs). Results 17 studies (22 740 patients) were included, 11 focusing on ACS (17 896 patients) and six on stable coronary disease (4844 patients). In the ACS subgroup, LMD or 3VD occurred in 20% (95% CI 7.2% to 33.4%), LMD in 12% (95% CI 10.5% to 13.5%), and 3VD in 25% (95% CI 23.1% to 27.0%). Heart failure at admission and extent of ST-segment elevation in lead aVR on 12-lead ECG were the most powerful predictors of LMD or 3VD. In the stable disease subgroup, LMD or 3VD was found in 36% (95% CI 18.5% to 48.8%), with the most powerful predictors being transient ischaemic dilation during the imaging stress test, extent of ST-segment elevation in aVR and V1 during the stress test, and hyperlipidaemia. Conclusions This meta-analysis demonstrated that severe coronary diseasedthat is, LMD or 3VDdis more common in patients with ACS or stable coronary disease than generally perceived, and that simple and low-cost tools may help in the selection of the most appropriate therapeutic approach. [ABSTRACT FROM AUTHOR]

Objectives: This study tested the hypothesis that 4-[18F]fluorophenyltriphenylphosphonium (18F-TPP) is useful for in vivo positron emission tomography (PET) measurement of mitochondrial membrane potential (ΔΨm). Its utility as a blood flow tracer also was evaluated. Background: Tetraphenylphosphonium is useful for in vitro measurement of ΔΨm. In vivo measurement of ΔΨm has potential value in the assessment of heart failure pathophysiology and therapy as well as assessment of myocardial viability and so may be a very useful clinical tool. Methods: Anesthetized swine (N = 6) with a balloon catheter in the left anterior descending coronary artery were studied. Microsphere measurements of myocardial blood flow (MBF) were made after balloon inflation (baseline) and ∼10 min after intravenous administration of adenosine and phenylephrine after which ∼10 mCi 18F-TPP was injected intravenously and dynamic PET data acquisition obtained for 30 min. After the swine were killed, the hearts were sectioned for microsphere measurement of MBF and 18F-TPP measured by well counter in these same samples. PET images provided whole blood and myocardial 18F-TPP concentration for determination of ΔΨm by the Nernst equation, corrected for nonspecific 18F-TPP binding. Microsphere MBF, absolute (ml/min/g) and relative, was compared with PET data (standard uptake value and K1). Results: Nonspecific binding of 18F-TPP overestimated ΔΨm measured by −37 ± 4 mV (mean ± SD). Normal zone ΔΨm of ex vivo samples (−91 ± 11 mV; N = 52; sample weight, 1.07 ± 0.18 g) correlated strongly (R2= 0.93) with normal zone by PET (−81 ± 13 mV). Both ex vivo and PET normal zone ΔΨm, although somewhat lower, compared well with that reported for tritium labeled triphenylphosphonium in normal working Langendorff rat heart (−100 mV). Although the relative MBF by 18F-TPP correlated strongly with relative microsphere MBF (R2= 0.83), there was no correlation between absolute MBF by 18F-TPP and microsphere MBF. Conclusions: 18F-TPP is a promising tracer for noninvasive PET measurement of ΔΨm in living subjects. It is useful as well for assessment of relative but not absolute MBF. [Copyright &y& Elsevier]

Current American Heart Association/American College of Cardiology practice guidelines classify congestive heart failure (CHF) in 4 stages (A, B, C, and D). This review focuses on state-of-the-art and future applications of quantitative positron emission tomography (PET) myocardial perfusion and metabolic imaging in the clinical evaluation and treatment of patients in all CHF stages. Basic physiological and metabolic principles related to the regulation of myocardial blood flow and metabolism at various stages of CHF are briefly reviewed. The advantages of quantitative PET image analysis in contrast to simple qualitative visual analysis of the scans also will be addressed. Finally, potential future clinical applications of quantitative PET for CHF evaluation and treatment will be discussed. [ABSTRACT FROM AUTHOR]

Objectives: The authors tested the hypothesis that exercise treadmill testing (ETT)–induced ST-segment elevation (STE) in electrocardiographic lead aVR is an important indicator of significant left main coronary artery (LMCA) or ostial left anterior descending coronary artery (LAD) stenosis. Background: Although STE in lead aVR is an indicator of LMCA or very proximal LAD occlusion in acute coronary syndromes, its predictive power in the setting of ETT is uncertain. Methods: Rest and stress electrocardiograms, clinical and stress test parameters, and single photon-emission computed tomographic myocardial perfusion imaging (MPI) data, when available, were obtained in 454 subjects (378 with MPI) who underwent cardiac catheterization and standard Bruce ETT ≤ 6 months before catheterization. Patients were selected for LMCA or ostial LAD disease (≥50% stenosis) with or without other coronary artery disease (CAD), CAD (≥70% stenosis) without significant LMCA or ostial LAD, or no significant CAD. Univariate followed by multivariate logistic regression analyses of clinical, electrocardiographic, stress test, and single photon-emission computed tomographic MPI variables were used to identify significant correlates of LMCA or ostial LAD stenosis. Bayesian analysis of the data also was performed. Results: LMCA (n = 38) or ostial LAD (n = 42) stenosis occurred in 75 patients (5 patients had both). The remainder had CAD without LMCA or ostial LAD stenosis (n = 276) or no CAD (n = 103). In multivariate analysis, the strongest predictor was stress-induced STE in lead aVR (p < 0.0001, area under the curve 0.82). Both left ventricular ejection fraction (after stress) and percent reversible LAD ischemia on single photon-emission computed tomographic MPI also contributed significantly in multivariate analysis (p < 0.005 and p < 0.05, respectively, areas under the curve 0.60 and 0.64, respectively). Although additional electrocardiographic, stress test, and MPI variables were significant univariate predictors, none was statistically significant in multivariate analysis. At 1-mm STE in lead aVR, sensitivity for LMCA or ostial LAD stenosis was 75%, specificity was 81%, overall predictive accuracy was 80%, and post-test probability increased nearly 3 times from 17% to 45%. Conclusions: Stress (ETT)–induced STE in lead aVR is an important indicator of significant LMCA or ostial LAD stenosis and should not be ignored. [Copyright &y& Elsevier]

Objectives: This study tests the hypothesis that absolute measurement of adenosine (Ado)-stimulated myocardial blood flow (MBFado) is superior to measurement of relative tracer uptake for identification of hemodynamically significant coronary artery disease (CAD). Background: Positron emission tomography measurement of absolute myocardial blood flow (MBF) (13N-ammonia) with Ado has the capability to more accurately assess hemodynamic severity of CAD than measurement of relative tracer content (TC) (nCi/ml) during Ado, which by definition depends on at least 1 normal zone to which others are compared. Methods: A total of 27 patients (20 male, 58 ± 11 years, mean ± SD) with known or suspected CAD and 21 normal subjects (13 male, 38 ± 10 years) were studied. Parametric (K1) MBF images and TC sum images were analyzed. A stenosis ≥70% defined significant CAD. The receiver-operator characteristic curve (ROC) analysis area under the curve (AUC) compared MBF and TC results. Cut-point analysis for sensitivity, specificity, and accuracy showed the best MBF criteria for CAD as MBFado <1.85 ml/min/g and the best TC as <70% maximum. The myocardial blood flow reserve ratio (MBFR) (optimal <2.0×) also was studied. Results: The ROC analysis of PET parameters showed that MBFado was superior to <70% maximum uptake for CAD detection (n = 144 vessels; AUC 0.900 vs. 0.690, respectively, p < 0.0001) and was marginally greater than MBFR (0.856; p = 0.10). For CAD cut-point analysis, MBFado accuracy exceeded TC (0.84 vs. 0.72, respectively, p = 0.005), as did sensitivity (0.81 vs. 0.48, respectively; p = 0.001). Specificity of MBFado for CAD classification (0.85) was comparable to TC (0.82; p = NS). Sensitivity, specificity, and predictive accuracy for MBFR were 0.62, 0.85, and 0.79, respectively. The difference in specificity was not significant versus MBFado. However, MBFado was more sensitive than MBFR (p = 0.01). The difference in predictive accuracy was borderline (p = 0.06) in favor of MBFado. Conclusions: Measurement of Ado-stimulated absolute MBF is superior to relative measurement of myocardial tracer retention for identification of CAD and can be accomplished with a single MBFado measurement. [Copyright &y& Elsevier]