Review ArticleRadionuclide noninvasive evaluation of heart failure beyond left ventricular function assessment
Introduction
Heart failure (HF) is a complex clinical syndrome characterized by dyspnea, fatigue, and fluid retention, which results from any structural or functional cardiac disorder that impairs the ability of the left ventricle (LV) to fill with or eject blood. It is a common, costly, disabling, and potentially fatal disorder. The prevalence and incidence of HF are increasing rapidly in the Western world because of the aging of the population and an ever-increasing number of survivals to acute coronary syndromes (CAD is the most prevalent underlying etiology, affecting about 70% of cases), despite advances in different pharmacological and nonpharmacological therapies.
The development of HF initiates with some injury to, or stress on, the myocardium, which usually produces progressive changes in the geometry and structure of the LV, with pathologic hypertrophic growth. This pathologic remodeling involves a shift toward glycolytic metabolism, disorganization of the sarcomere, alterations in calcium handling, changes in contractility, loss of myocytes with fibrotic replacement, LV dilatation, systolic or diastolic dysfunction, and electrical remodeling (i.e., alterations in the expression or function of ion transporting proteins, or both) with propensity to malignant ventricular arrhythmia.
Patients with HF have elevated circulating or tissue levels of norepinephrine (NE), angiotensin II, aldosterone, endothelin, vasopressin, and cytokines. Initially after the onset of HF, enhanced sympathetic nervous system activity is responsible for the increase in heart rate, contractility, venous return, and systemic arterial constriction, thus supporting the cardiovascular system to preserve organ perfusion. However, chronic activation of endogenous neurohormonal systems has deleterious effects on the cardiovascular system. Activation of the renin-angiotensin system (RAS) not only increase the hemodynamic stresses and energetic requirements of the LV by causing sodium retention and peripheral vasoconstriction, but may also exert direct noxious effects on cardiomyocytes (apoptosis and regression to a fetal phenotype) and changes in the nature of the extracellular matrix (stimulation of myocardial fibrosis), which can further alter the architecture and impair the performance of the failing heart (Figure 1).
Although the basic characterization of patients with HF is supported primarily by echocardiographic assessment of the LV function, other noninvasive imaging procedures related with the detection of the different causes of HF and their respective consequences on the myocardium have been developed or are under development, including those involved in the study of myocardial perfusion, metabolism, cellular injury, intersticial dysregulation, and neurohormonal receptor function. Nuclear imaging techniques are the only imaging techniques with sufficient sensitivity to assess processes that take place at picomolar concentrations in the human heart.1, 2, 3 Nuclear techniques for molecular imaging of the myocardium may provide valuable insights into the pathophysiology, severity, management (medical/mechanical/surgical), response to treatment, and prognosis of HF patients. This will permit individualized management decisions and hopefully facilitate better clinical outcomes for patients with HF.
Section snippets
Imaging Myocardial Perfusion and Coronary Vessels
Coronary artery disease (CAD) is the most frequent cause of HF in developed countries. Myocardial perfusion single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging at rest and stress can identify those patients with HF who have potentially ischemic reversible LV dysfunction and in whom revascularization may be indicated.4 In this setting, a normal stress perfusion study has high negative predictive value for the presence of significant CAD. However,
Imaging Myocardial Metabolism
Energy supply to normal oxygenated myocardium under fasting conditions is provided by β-oxidation of free fatty acids (60-90% of ATP production) and glycolysis (10-40% of ATP production). Both routes result in acetyl coenzyme A, which is subsequently metabolized into carbon dioxide and water via tricarboxylic acid cycle (Krebs cycle).7 Each metabolic pathway can be assessed by nuclear techniques.
Myocytes of patients with HF show reduced mechanical efficiency associated with depletion of
Imaging Myocardial Injury
Reduction of myocardial injury and timely intervention after the influence of different noxious agents on the myocardium keep on being the goal of prevention of HF, since cardiomyocytes are not capable of regeneration and loss of contractile myocardial mass is directly related to prognostic outcomes.18 Therefore, development of noninvasive tests for detection of myocardial injury is of extreme importance. An imaging technique that identifies cell injury rapidly could facilitate clinical
Imaging Myocardial Interstitial Dysregulation
Research in HF has principally focused on cardiomyocytes, although they account for only one-third of myocardial cells.45 Both myocyte and collagen compartments are involved in the process of ischemic cardiomyopathy and probably in other cardiomyopathies. In the future, assessment of molecules associated with modifications in myocardial interstitium may provide novel insights to further guide the management of patients with HF, enabling a more sophisticated distinction between cardiomyopathies,
Imaging Myocardial Neurohormonal Axis
Persistently activated sympathetic nervous system and of the RAS are both closely related with the gross, cellular, and molecular changes that are characteristic of LV remodeling (Figure 1).
Imaging Cell-Based Therapy
Cell transplantation has shown potential to repair the injured myocardium in patients with HF. Methods to monitor cell migration, homing, survival, and engraftment may facilitate the understanding of heterogeneous results from early clinical investigations of transplantation of stem progenitor cells (SPCs). Noninvasive in vivo imaging of cell-based therapy outcomes includes visualization of SPCs early after transplantation, as well as monitoring their survival, proliferation, and
Conclusions
Currently, the management of patients with HF is supported primarily by echocardiographic assessment of the LV function. However, other noninvasive imaging procedures related with the detection of the different causes and consequences of HF on the myocardium have been developed or are under development, including those involved in the study of myocardial perfusion, metabolism, cellular injury, interstitial dysregulation, and neurohormonal receptor function. Nuclear cardiology is the only
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