Despite many advances in therapy, chronic heart failure remains a prevalent condition with a high mortality rate.¹ The successful treatment of heart failure patients requires establishing an accurate diagnosis, identifying potentially reversible etiologies, determining the optimal therapy, and reliable risk assessment for stratification of patients at high risk for worsening. Several of these aspects of heart failure care can be gainfully evaluated via radionuclide imaging. This chapter will review established applications of radionuclide imaging in heart failure.

The clinician has several goals when evaluating a heart failure patient. One potential work flow sequence for the evaluation of newly diagnosed heart failure is shown in Figure 18-1. Once a clinical diagnosis of the syndrome of heart failure is made, an initial step is often the determination of left ventricular (LV) systolic function. Approximately one-half of patients will have heart failure with preserved ejection fraction (HFpEF, EF ≥40%), while the remainder will have LV systolic dysfunction (heart failure with reduced ejection fraction HFrEF, EF <40%).² Radionuclide imaging methods including single-photon emission computed tomography (SPECT), radionuclide ventriculography (RVG), and positron emission tomography (PET) can all provide highly accurate and repeatable measures of LV systolic and diastolic function (Chapter 11). Despite being as prevalent as HFrRF, the treatment of HFpEF remains largely symptom based and empirical, with very little supportive data from clinical trials. For patients with systolic dysfunction, HFrEF, a critical next step is the determination of etiology. Etiology evaluation can include identifying specific and potentially remediable causes such as valvular disease, coronary artery disease (CAD), specific cardiomyopathies, and pericardial disease. When extensive CAD is found, testing for ischemia and viability is helpful to determine benefit from coronary revascularization. Radionuclide imaging has critical roles in the determination of heart failure etiology (see below), identifying patients for coronary revascularization (Chapter 21), and the evaluation for specific cardiomyopathies such as amyloidosis and sarcoidosis (Chapter 24). For patients with nonischemic cardiomyopathy (NICM), and those with persistent LV systolic dysfunction after specific intervention, a combination of guideline-directed medical therapy (GDMT), and device therapy in selected patients (implantable cardioverter defibrillator [ICD], and cardiac resynchronization therapy [CRT]), form the cornerstone of current recommendations. Evolving applications such as myocardial sympathetic neuronal function (Chapter 23) and dyssynchrony imaging (Chapter 11) may have relevance to the selection of patients for ICD and CRT. Furthermore, PET/CT imaging with F-18 fluorodeoxyglucose (FDG) has established utility in the challenging area of diagnosing device infections (Chapter 24). A minority of patients will receive advanced heart failure therapies, including left and right ventricular assist devices (LVAD and RVAD) and cardiac transplantation. In posttransplant patients, radionuclide imaging has important prognostic value, which may influence therapeutic options in patients with suspected allograft vasculopathy (see below).

Determination of Heart Failure Etiology

The etiology of heart failure varies considerably depending on the population studied.³ Based on clinical trial data on patients with established heart failure, CAD is the attributed etiology for 60% to 70% of heart failure in the United States.⁴ However, the mere presence of CAD in the setting of a cardiomyopathy does not imply an ischemic etiology to the LV dysfunction. What is traditionally referred to as significant CAD in the literature, that is, ≥50% luminal stenosis, may be encountered in 15% to 30% of patients with a dilated cardiomyopathy, and thus may not be sufficiently sensitive for accurate risk stratification of the heart failure population. Felker et al. addressed this question, and tested a more stringent definition of ischemic cardiomyopathy for characterization of heart failure patients.⁵ They defined ischemic cardiomyopathy as LV dysfunction with one or more of the following angiographic criteria: significant left main or proximal left anterior descending coronary artery stenosis, at least two-vessel disease with ≥70% stenosis, or single-vessel disease with prior myocardial infarction, or prior coronary revascularization. For example, a patient with LV dysfunction and a 70% stenosis of one major epicardial vessel without antecedent myocardial infarction or revascularization would be adjudicated to the nonischemic cardiomyopathy group (with coexisting, but not causally related CAD). Using these more restrictive criteria, patients with LV dysfunction and single-vessel CAD had a prognosis comparable to those with nonischemic cardiomyopathy.⁵ Patients with true CAD-related heart failure have a worse prognosis than those with nonischemic cardiomyopathy, but the former may improve cardiac function dramatically with revascularization, highlighting the critical importance of an accurate diagnosis. The literature regarding the use of SPECT for the diagnosis of underlying CAD in LV dysfunction has primarily focused upon patients with chronic heart failure, with scant data addressing the diagnosis of CAD in new-onset heart failure.

In the setting of newly diagnosed LV systolic dysfunction, the identification of underlying CAD and potential “at risk” dysfunctional myocardium that might recover with coronary revascularization is critical. Although current practice guidelines specifically mandate coronary angiography only in heart failure patients with angina, chest pain is often absent in patients with ischemic cardiomyopathy, even those with significant amounts of viable myocardium.^2,6

The Investigation of Myocardial Gated SPECT Imaging (IMAGING) in Heart Failure trial specifically addressed the utility of gated SPECT as an initial diagnostic modality in the de novo acute heart failure setting.⁷ Two hundred and one patients hospitalized with new-onset heart failure were prospectively enrolled, and underwent exercise or pharmacologic SPECT during the index hospitalization. At the physician’s discretion, approximately one-third of the patients underwent coronary angiography. Using a summed stress score (SSS) >3 to define an abnormal study, SPECT had a sensitivity of 96% and a negative predictive value of 96% for the diagnosis of ischemic cardiomyopathy using the criteria proposed by Felker, but was less accurate in detecting limited-extent CAD (Table 18-1). Thus, this study provides proof of concept of the utility of myocardial SPECT for the initial characterization of patients presenting with severe new-onset heart failure. Such patients who have normal stress myocardial SPECT are very unlikely to have underlying extensive CAD that is etiologically related to their heart failure (Fig. 18-2).

Several previous studies have established the utility of myocardial perfusion imaging (MPI) for the diagnosis of CAD in chronic heart failure.⁸ Although many of these studies predated contemporary MPI, they uniformly demonstrated a very high negative predictive value for excluding CAD. Using more contemporary imaging with gated Tc-99m SPECT, Danias et al. reported an SSS >8 as 87% sensitive for detection of CAD, and that incorporating the SDS with findings of ischemia and regional wall motion abnormalities increased this to 94%.⁹ Thus, in the setting of both new-onset and established heart failure, and global dysfunction, a normal stress myocardial perfusion scan virtually excludes a diagnosis of ischemic LV dysfunction.