The Changing Face of Nuclear Cardiology: Guiding Cardiovascular Care Toward Molecular Medicine

Abstract

Radionuclide imaging of myocardial perfusion, function, and viability has been established for decades and remains a robust, evidence-based and broadly available means for clinical workup and therapeutic guidance in ischemic heart disease. Yet, powerful alternative modalities have emerged for this purpose, and their growth has resulted in increasing competition. But the potential of the tracer principle goes beyond the assessment of physiology and function, toward the interrogation of biology and molecular pathways. This is a unique selling point of radionuclide imaging, which has been underrecognized in cardiovascular medicine until recently. Now, molecular imaging methods for the detection of myocardial infiltration, device infection, and cardiovascular inflammation are successfully gaining clinical acceptance. This is further strengthened by the symbiotic quest of cardiac imaging and therapy for an increasing implementation of molecule-targeted procedures, in which specific therapeutic interventions require specific diagnostic guidance toward the most suitable candidates. This review will summarize the current advent of clinical cardiovascular molecular imaging and highlight its transformative contribution to the evolution of cardiovascular therapy beyond mechanical interventions and broad blockbuster medication, toward a future of novel, individualized molecule-targeted and molecular imaging-guided therapies.

Keywords: cardiovascular infection; infiltrative cardiomyopathy; inflammation; molecular imaging; nuclear cardiology.

FIGURE 1.

Growing role of molecule-targeted therapy in cardiovascular medicine. Targeted therapy is increasingly implemented to support and supplant broad blockbuster drug therapy and mechanical intervention, requiring specific guidance to the right patient at the right time—guidance that may be obtained by molecular imaging.

FIGURE 2.

Growing role of molecule-targeted cardiovascular imaging, as supported by success of molecular medicine in other areas such as oncology and neurology, serving as role model and providing innovative targets and tracers (A); increasing role of molecule-targeted therapies in cardiology, leading to increasing demand for biomarkers (B); and strong role and further evolution of conventional noninvasive imaging of morphology, physiology, and function, providing high-end methodology and correlative imaging information (C).

FIGURE 3.

¹⁸F-FDG PET/CT of cardiovascular device infection. (A) Prosthetic valve endocarditis: CT, PET, and PET/CT fusion images in representative transaxial and coronal views, along with whole-body maximum-intensity projection (MIP). Intense uptake is present at aortic valve prosthesis, implanted 2 y previously. MIP shows additional focal ¹⁸F-FDG–avid embolus in right lower leg (arrow). (B) Left-ventricular assist device infection. Intense uptake is seen around device and outflow tract in left chest wall (left) and along driveline (right) in patient with diffuse reddening and swelling of left chest wall and purulent drainage at entry side of driveline. MIP shows additional uptake in reactive mediastinal lymph nodes.

FIGURE 4.

Molecular imaging of cardiac amyloidosis. (A) Scintigraphy with bone-seeking tracer ^99mTc-diphosphonopropanodicarboxylic acid (^99mTc-DPD) in patient with wild-type ATTR. Shown are planar whole-body image; transaxial CT, SPECT, and SPECT/CT fusion images; and reoriented cardiac images in short-axis (SA), horizontal long-axis (HLA), and vertical long-axis (VLA) views using dedicated cadmium-zinc telluride (CZT) camera. Significant tracer uptake is identified in heart, exceeding bone uptake (Perugini score, 3). Tomographic images show strongest signal in septum. In absence of serum light chains, findings are consistent with cardiac ATTR. (B) PET scan with amyloid marker ¹⁸F-florbetapir in patient with light-chain amyloidosis. Whole-body maximum-intensity projection (MIP) shows diffuse bone marrow uptake consistent with involvement of hematopoietic system. Tomographic cardiac images show diffuse myocardial uptake consistent with cardiac light-chain amyloidosis.

FIGURE 5.

¹⁸F-FDG PET/CT in cardiac sarcoidosis. (A) Representative transaxial CT, PET, and PET/CT fusion images of cardiac region (left) showing strongly increased septal uptake consistent with biopsy-proven active cardiac sarcoidosis. Images of lung region (right), along with whole-body maximum-intensity projection (MIP), show mild, diffuse uptake in both lung lobes indicating moderately active pulmonary sarcoidosis. (B) Integration with cardiac MRI (CMR), showing transmural late gadolinium enhancement in anterior wall, septum, and anterior portion of right ventricle, colocalizing with ¹⁸F-FDG uptake in reangulated short-axis PET/CT images.

FIGURE 6.

¹⁸F-FDG PET/CT of vascular inflammation. (A) Vascular graft infection. CT, PET, and PET/CT fusion images in representative transaxial and coronal views, along with whole-body maximum-intensity projection (MIP), 12 mo after endovascular aortic repair for aneurysm of descending thoracic aorta. CT is consistent with endoleak of prosthesis, leading to expanding aneurysm, and PET shows intense uptake in periphery of aneurysm, consistent with infection, requiring surgical revision. (B) Large-vessel vasculitis. Shown are representative images in patient with weight loss, elevated level of serum C-reactive protein, and fever of unknown origin. Intense, diffuse elevated uptake in walls of aorta, large arteries of neck, and upper and lower extremities (significantly above liver uptake) is consistent with active giant-cell arteritis.

FIGURE 7.

Key principle of systems-based, image-guided (molecular) therapy in cardiovascular medicine. Cardiovascular target tissue interacts with remote tissue through various molecular mechanisms, which underlie temporal dynamics and can be targeted by molecular imaging agents. Imaging may identify dysregulation of target mechanism, which indicates risk for adverse outcome. This information may trigger targeted therapy to adjust target mechanism, improve disease course, and achieve favorable outcome.