The role of nuclear imaging in the failing heart: myocardial blood flow,sympathetic innervation,and future applications

Heart failure represents a common disease affecting approximately 5 million patients in the United States. Several conditions play an important role in the development and progression of heart failure, including abnormalities in myocardial blood flow and sympathetic innervation. Nuclear imaging represents the only imaging modality with sufficient sensitivity to assess myocardial blood flow and sympathetic innervation of the failing heart. Although nuclear imaging with single-photon emission computed tomography (SPECT) is most commonly used for the evaluation of myocardial perfusion, positron emission tomography (PET) allows absolute quantification of myocardial blood flow beyond the assessment of relative myocardial perfusion. Both techniques can be used for evaluation of diagnosis, treatment options, and prognosis in heart failure patients. Besides myocardial blood flow, cardiac sympathetic innervation represents another important parameter in patients with heart failure. Currently, sympathetic nerve imaging with 123-iodine metaiodobenzylguanidine (123-I MIBG) is often used for the assessment of cardiac innervation. A large number of studies have shown that an abnormal myocardial sympathetic innervation, as assessed with 123-I MIBG imaging, is associated with increased mortality and morbidity rates in patients with heart failure. Also, cardiac 123-I MIBG imaging can be used to risk stratify patients for ventricular arrhythmias or sudden cardiac death. Furthermore, novel nuclear imaging techniques are being developed that may provide more detailed information for the detection of heart failure in an early phase as well as for monitoring the effects of new therapeutic interventions in patients with heart failure.     

Clinical use of nuclear cardiology in the assessment of heart failure

A nuclear cardiology test is the most commonly performed non-invasive cardiac imaging test in patients with heart failure, and it plays a pivotal role in their assessment and management. Quantitative gated single positron emission computed tomography (QGS) is used to assess quantitatively cardiac volume, left ventricular ejection fraction (LVEF), stroke volume, and cardiac diastolic function. Resting and stress myocardial perfusion imaging, with exercise or pharmacologic stress, plays a fundamental role in distinguishing ischemic from non-ischemic etiology of heart failure, and in demonstrating myocardial viability. Diastolic heart failure also termed as heart failure with a preserved LVEF is readily identified by nuclear cardiology techniques and can accurately be estimated by peak filling rate (PFR) and time to PFR. Movement of the left ventricle can also be readily assessed by QGS, with newer techniques such as three-dimensional, wall thickening evaluation aiding its assessment. Myocardial perfusion imaging is also commonly used to identify candidates for implantable cardiac defibrillator and cardiac resynchronization therapies. Neurotransmitter imaging using (123)I-metaiodobenzylguanidine offers prognostic information in patients with heart failure. Metabolism and function in the heart are closely related, and energy substrate metabolism is a potential target of medical therapies to improve cardiac function in patients with heart failure. Cardiac metabolic imaging using (123)I-15-(p-iodophenyl)3-R, S-methylpentadecacoic acid is a commonly used tracer in clinical studies to diagnose metabolic heart failure. Nuclear cardiology tests, including neurotransmitter imaging and metabolic imaging, are now easily preformed with new tracers to refine heart failure diagnosis. Nuclear cardiology studies contribute significantly to guiding management decisions for identifying cardiac risk in patients with heart failure.     

PCSK9 Inhibitors: Potential in Cardiovascular Therapeutics

Heart failure is a serious condition with poor prognosis, which imposes an ever increasing burden on healthcare systems due to its rising prevalence. Nonetheless, physiological processes underlying heart failure remain poorly understood. In recent years, functional imaging such as gated CT has become available for routine clinical cardiology investigations. However, a maturation of nuclear imaging techniques such as PET and SPECT is now yielding new insights into the pathophysiological changes underlying heart failure, based on non-invasive measurements of myocardial blood flow, myocardial viability, sympathetic innervation, neoangiogenesis and matrix metalloproteinases activity. Investigations of these biomarkers have the potential to reveal early aspects of left ventricle remodeling; diagnosis at an earlier stage of heart failure promises to facilitate improved intervention and therapy guidance. Furthermore, nuclear imaging techniques are being developed to monitor and predict outcome of novel cell-based approaches for restorative therapy of heart failure.     

Left ventricular dyssynchrony in patients with heart failure: pathophysiology, diagnosis and treatment

The number of patients with chronic heart failure is increasing rapidly in the Western world. Despite the introduction of new pharmacologic therapies, the prognosis of these patients remains poor. Left ventricular (LV) dyssynchrony is a frequently observed feature in patients with heart failure, and is recognized as an important predictor of poor outcome if left untreated. The presence of LV dyssynchrony leads to inefficient LV contraction with a decreased cardiac output. Moreover, patients with LV dyssynchrony are at increased risk of adverse cardiac events. New therapeutic options targeted at restoring normal mechanical synchrony, such as cardiac resynchronization therapy, have been shown to improve clinical symptoms and prognosis in patients with heart failure. The beneficial effects of cardiac resynchronization therapy are predominantly mediated by this treatment's ability to reduce LV dyssynchrony. Given these results, adequate identification of LV dyssynchrony in patients with heart failure is of paramount importance. Several new imaging techniques are proving useful for diagnosis of LV dyssynchrony. In particular, advanced echocardiographic techniques (e.g. tissue Doppler imaging) and conductance catheter techniques are two accurate methods for quantification of LV dyssynchrony. In this review, we discuss the pathophysiology, diagnosis and treatment of LV dyssynchrony in patients with heart failure.     

Reclassifying heart failure: predominantly subendocardial, subepicardial, and transmural

Recent innovations in imaging techniques have provided key mechanistic insights into the diverse phenotypic expressions of heart failure, with a wide range of potential applications to uncover the stages in progression of cardiac muscle dysfunction. This review proposes a new algorithm for exploring the spectrum of altered cardiac muscle mechanics in patients with heart failure.     

Adipositas und Herzinsuffizienz

Obesity doubles the risk of heart failure independent of comorbidities like hypertension or coronary artery disease potentially mediated by altered hemodynamics to compensate increased mass and metabolic activity. Symptoms of obesity cardiomyopathy do not differ from other forms of cardiomyopathy, but may be easily mixed up with obesity associated symptoms. The diagnosis can be made with imaging techniques like echocardiography or magnetic resonance imaging. Therapeutic approaches include weight control by dietary intervention and exercise, as well as bariatric surgery for the morbidly obese. Heart failure treatment should otherwise follow the general heart failure guidelines.     

Obesity and heart failure

Obesity doubles the risk of heart failure independent of comorbidities like hypertension or coronary artery disease potentially mediated by altered hemodynamics to compensate increased mass and metabolic activity. Symptoms of obesity cardiomyopathy do not differ from other forms of cardiomyopathy, but may be easily mixed up with obesity associated symptoms. The diagnosis can be made with imaging techniques like echocardiography or magnetic resonance imaging. Therapeutic approaches include weight control by dietary intervention and exercise, as well as bariatric surgery for the morbidly obese. Heart failure treatment should otherwise follow the general heart failure guidelines.     

Atherosclerosis imaging and heart failure

Coronary atherosclerosis is the most important primary etiologic factor predisposing to the development of heart failure. The mechanisms by which coronary atherosclerosis lead to heart failure likely involve the initial development of regional myocardial dysfunction, later progressing to global ventricular failure and symptomatic congestive disease. A variety of imaging strategies have been investigated for their value in identifying and characterizing markers of atherosclerosis in the effort to detect early cardiac disease. Non-invasive imaging techniques for assessing anatomic or functional manifestations of atherosclerosis include carotid ultrasonography, coronary computed tomography, cardiovascular magnetic resonance imaging, brachial artery reactivity testing, and the ankle-brachial index. Many of these imaging methods are shown to have accuracy, reliability, and the potential to add value to an office-based cardiovascular risk assessment. Further development of such imaging methods could facilitate early intervention in the development of myocardial dysfunction while enhancing our understanding of the natural course of atherosclerotic disease.     

Cardiac Ultrasound Imaging in Heart Failure: Recent Advances

Several new imaging modalities are being utilized in the management of heart failure. Echocardiography and speckle tracking imaging offer clinician the benefits of easy accessibility, real time data interpretation and objective quantification of heart function. Accordingly, this article reviews the current evidence base related to the use of echocardiography and other advanced ultrasonography techniques in heart failure, and discusses applications as well as limitations of these emerging technologies. The role of cardiac resynchronization therapy (CRT) and implications of the PROSPECT (Predictors of Response to CRT) trial in management of heart failure are also reviewed. The article concludes with a discussion about the evolving role of echocardiography in diagnosis and management of subclinical heart disease, so that preventive strategies may be devised.     

Clinical approaches to the diagnosis of acute heart failure

PURPOSE OF REVIEW: Predicting which patients with congestive heart failure will decompensate is often difficult, and it is often difficult to distinguish congestive heart failure from other causes of acute dyspnea. This review will focus on some of the newer tools used to diagnose acute congestive heart failure in addition to reviewing the utility of more traditional tools. RECENT FINDINGS: The integration of pertinent positives and negatives on a routine history, key physical findings on examination and routine noninvasive imaging offers high positive and negative predictive power for the diagnosis of acute heart failure. Measurement of B-type natriuretic peptide and N-terminal proB-type natriuretic peptide offers additional and incremental diagnostic information. Measurement of intrathoracic impedance is a novel and potentially useful tool to track absolute changes in cardiac function and total lung fluid content, and may be useful for the outpatient titration of medical therapy to minimize acute congestive heart failure decompensation. SUMMARY: Consistent accurate diagnosis of decompensated congestive heart failure is possible using no more than a complete history and physical examination along with routine imaging techniques. The ability to diagnose acute congestive heart failure however, is improved by using serum B-type natriuretic peptide and intrathoracic impedance, both of which offer additive and complementary diagnostic information.     

Imaging in patients with suspected acute heart failure: timeline approach position statement on behalf of the Heart Failure Association of the European Society of Cardiology

Acute heart failure is one of the main diagnostic and therapeutic challenges in clinical practice due to a non‐specific clinical manifestation and the urgent need for timely and tailored management at the same time. In this position statement, the Heart Failure Association aims to systematize the use of various imaging methods in accordance with the timeline of acute heart failure care proposed in the recent guidelines of the European Society of Cardiology. During the first hours of admission the point‐of‐care focused cardiac and lung ultrasound examination is an invaluable tool for rapid differential diagnosis of acute dyspnoea, which is highly feasible and relatively easy to learn. Several portable and stationary imaging modalities are being increasingly used for the evaluation of cardiac structure and function, haemodynamic and volume status, precipitating myocardial ischaemia or valvular abnormalities, and systemic and pulmonary congestion. This paper emphasizes the central role of the full echocardiographic examination in the identification of heart failure aetiology, severity of cardiac dysfunction, indications for specific heart failure therapy, and risk stratification. Correct evaluation of cardiac filling pressures and accurate prognostication may help to prevent unscheduled short‐term readmission. Alternative advanced imaging modalities should be considered to assist patient management in the pre‐ and post‐discharge phase, including cardiac magnetic resonance, computed tomography, nuclear studies, and coronary angiography. The Heart Failure Association addresses this paper to the wide spectrum of acute care and heart failure specialists, highlighting the value of all available imaging techniques at specific stages and in common clinical scenarios of acute heart failure.     

Comprehensive in‐hospital monitoring in acute heart failure: applications for clinical practice and future directions for research. A statement from the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

This paper provides a practical clinical application of guideline recommendations relating to the inpatient monitoring of patients with acute heart failure, through the evaluation of various clinical, biomarker, imaging, invasive and non‐invasive approaches. Comprehensive inpatient monitoring is crucial to the optimal management of acute heart failure patients. The European Society of Cardiology heart failure guidelines provide recommendations for the inpatient monitoring of acute heart failure, but the level of evidence underpinning most recommendations is limited. Many tools are available for the in‐hospital monitoring of patients with acute heart failure, and each plays a role at various points throughout the patient's treatment course, including the emergency department, intensive care or coronary care unit, and the general ward. Clinical judgment is the preeminent factor guiding application of inpatient monitoring tools, as the various techniques have different patient population targets. When applied appropriately, these techniques enable decision making. However, there is limited evidence demonstrating that implementation of these tools improves patient outcome. Research priorities are identified to address these gaps in evidence. Future research initiatives should aim to identify the optimal in‐hospital monitoring strategies that decrease morbidity and prolong survival in patients with acute heart failure.     

Tissue Doppler imaging and left ventricular dyssynchrony in heart failure

BackgroundElectrical dyssynchrony is one of the main criteria for determining eligibility for cardiac resynchronization therapy (CRT). However, recent data support the use of mechanical rather than electrical dyssynchrony as the major criterion for receiving CRT.Methods and ResultsTissue Doppler imaging (TDI) is emerging as an indispensable tool for measuring and quantifying mechanical dyssynchrony in patients with advanced heart failure. TDI techniques for quantifying dyssynchrony include: tissue tracking, tissue velocity imaging, tissue synchronization imaging, and strain analysis. This review details the different techniques and discusses advantages and disadvantages of each. As TDI is incorporated into clinical practice, the ability to select patients who are most likely to improve after CRT should increase. TDI may also prove to be a useful tool for optimizing pacemaker settings in patients who do not improve after CRT.ConclusionOngoing research trials will further define the role of TDI in the clinical management of patients with heart failure.     

Non-Invasive Cardiac Evaluation in Heart Failure Patients Using Magnetic Resonance Imaging: A Feasibility Study

Background: To assess the feasibility of a fast, flow-insensitive magnetic resonance imaging (MRI) protocol in heart failure patients for the evaluation of cardiac function, cardiovascular anatomy, and myocardial viability. Methods and Results: Thirty-two consecutive patients with left ventricular (LV) systolic dysfunction and 13 control subjects were prospectively evaluated with MRI. The exam consisted of cine imaging with a steady-state free precession sequence, followed by time-resolved, three-dimensional angiography and delayed, contrast-enhanced imaging. Multiple LV parameters were evaluated, and the heart failure and control results were compared. In 12 patients, MRI-determined ejection fractions were compared to echocardiographic values. Additionally, a qualitative analysis of the cine images was performed. The cardiac MR evaluation yielded diagnostic-quality images in all subjects. Mean imaging time was 37 min. MRI demonstrated significant differences between the heart failure and control subjects in all parameters assessed (p < 0.05). MRI-determined ejection fractions correlated strongly with echocardiographic values (R = 0.75), although the limits of agreement were wide (−17.3%–18.3%). Conclusions: Using fast, flow-insensitive imaging techniques, MRI is feasible in heart failure for the derivation of more independent indices of cardiac status than any other non-invasive test. Although further investigation is warranted, MRI may prove uniquely helpful in heart failure diagnosis and management.     

Non-invasive methods in differentiating ischaemic from non-ischaemic cardiomyopathy. A review paper

Chronic heart failure is a common disorder associated with high mortality and morbidity. Patients' numbers and the burden placed on health care services increase as the average age of the population rises. Non-invasive imaging plays a central role in the correct diagnosis of heart failure, the determination of aetiology and prognosis, as well as the monitoring of ongoing therapy. In this review paper we critically summarize techniques that differentiate ischaemic from non-ischaemic cardiomyopathy. Coronary angiography has been used as the primary method for distinguishing ischaemic from non-ischaemic cardiomyopathy; while studies utilizing echocardiography, myocardial perfusion imaging or electron computed tomography and positron emission tomography, have played a substantial role. More recently, CMR and multislice computed tomography have demonstrated ability in initial functional assessment and in the determination of secondary causes of heart failure.     

Update on cardiac imaging techniques. Echocardiography, cardiac magnetic resonance and multidetector computed tomography

This review of progress in cardiac imaging techniques summarizes the most significant development reported in the last year on different echocardiographic techniques and their application in a range of settings, from the treatment of heart failure to their use in intraoperative monitoring and guiding interventional procedures. Large sections are devoted to recent developments in three-dimensional imaging and, because of its clinical importance, to magnetic resonance imaging. Finally, there is a comprehensive update on the use of multidetector computed tomography in cardiology.     

Imaging cardiac neuronal function and dysfunction

In recent years, the importance of alterations of cardiac autonomic nerve function in the pathophysiology of heart diseases including heart failure, arrhythmia, ischemic heart disease, and diabetes has been increasingly recognized. Several radiolabeled compounds have been synthesized for noninvasive imaging, including single photon emission CT and positron emission tomography (PET). The catecholamine analogue I-123 metaiodobenzylguanidine (MIBG) is the most commonly used tracer for mapping of myocardial presynaptic sympathetic innervation on a broad clinical basis. In addition, radiolabeled catecholamines and catecholamine analogues are available for PET imaging, which allows absolute quantification and tracer kinetics modeling. Postsynaptic receptor PET imaging added new insights into mechanisms of heart disease. These advanced imaging techniques provide noninvasive, repeatable in vivo information of autonomic nerve function in the human heart and are promising for providing profound insights into molecular pathophysiology, monitoring of treatment, and determination of individual outcome.     

Hypothalamic dysfunction in heart failure: pathogenetic mechanisms and therapeutic implications

Neurohumoral activation is an important feature of heart failure. Recent advances in molecular biology and imaging techniques permitted a better understanding of the central role that hypothalamus plays in the modulation of dysfunctional mechanisms, as well as the occurrence of comorbidities, such as depression, in heart failure patients. This review summarizes the commonly reported neural reflexes and molecular signaling pathways at the level of the hypothalamus along with the dysfunctional mechanisms within the paraventricular nucleus and other areas of the hypothalamus in heart failure and describes some relevant therapeutic implications.     

Cardiac imaging in heart failure in the personalized medicine era: Pathway to knowledge or Tiresias’ paradox?

Tiresias was the blind prophet of Apollo in Thebes. Tiresias is a symbolic figure, which embodies a paradox: he is blind in the physical sense, but his knowledge surpasses all, as opposed to Oedipus who cannot see despite having a good eyesight. Cardiac imaging can be considered the technological extension of human eyes, which has clearly revolutionised the diagnostic approach in Cardiology and specifically in heart failure. Echocardiography contributed to an approach focused on the ejection fraction (EF) which is the cornerstone of the most recent classifications of heart failure. The recent advances in cardiac imaging raised our ability to understand the aetiological roots of disease. However, the increasing amount of information generated by the plethora of diagnostic imaging techniques raises the challenge of clinical significance. The explosion of “big data” in cardiac imaging may also impact on classifications and nomenclature and on our ability to cluster and categorize, an exercise that is becoming remarkably challenging when the quest for the particular is taken to the extreme and the infinitesimal. The essence of cardiac conditions causing heart failure would probably not entirely captured by an approach only focused on the direct visualization of the heart. Delivery of personalized medicine would not be based only on cardiac imaging, but through an holistic approach which overcomes the mere assessment of empiric reality as it appears to our eyes through the lens of increasingly advanced diagnostic techniques.