Nuclear medicine is born as a medical specialty by the end of the 1940s when nuclear energy is first used with medical purposes. The year 1946 marks a historic landmark when the first radionuclides are ever produced in a first-of-its kind nuclear reactor.

At the end of the 1970s, with the arrival of gamma cameras, the very first articles on the study of the heart start being published. Our country pioneered the use of these imaging modalities in South America, and we started landing cardiologists to nuclear medicine departments to perform cardiology procedures under various situations.

It was then that training cardiologists in the use of radioisotopes and the analysis of those results gives birth to the cardiology medical subspecialty of nuclear cardiology.

All cardiology scientific societies support the development of this specialty. Thus, the SAC creates the first Nuclear Cardiology Council and the FAC immediately follows through. Afterwards, the very first nuclear cardiologists fresh out of these 2 societies will lay the foundations of the Argentine Society of Nuclear Cardiology (AACN) that, together with cardiology societies and the Argentine Society of Biology and Nuclear Medicine will support the scientific activity on nuclear cardiology.

The technologies currently available are:

1. The SPECT (single-photon emission computed tomography) gamma camera with the gated-SPECT technique uses radioactive isotopes of gamma rays for the simultaneous study of myocardial perfusion, left ventricular function, parietal motility, ejection fraction, and ventricular volumes both at rest and during exercise. These machines can perform radionuclide ventriculographies, and studies for the diagnosis and assessment of amyloidosis, and other cardiomyopathies.

2. The fast D-SPECT gamma camera also allows measuring coronary flow and coronary flow reserve (CFR).

3. PET (positron emission tomography) uses isotopes of very short half-life to study feasibility, flow, CFR, and infections (endocarditis and device-related infections), and cardiac sarcoidosis.

The presence of the cardiologist at the nuclear medicine lab is essential because of his knowledge of diseases and anatomy, which optimizes the assessment of the patient and the interpretation of the study.

Knowing the shape and motility of the ventricle, whether there is ventricular remodeling or not, and motility segmental disorders associated with coronary anatomy is essential to achieve diagnosis. Flow impairment is interpreted based on the different arterial territories involved.

Afterwards, computed tomography-based attenuation correction and image fusions between 2 studies were born to achieve greater anatomical and functional correlations such as PET images with coronary computed tomography angiography (CCTA)

During these same decades, the field of interventional cardiologist will witness the birth of balloon angioplasties that will become a popular procedure of cath labs everywhere.

Ever since then, there has been a close correlation among nuclear cardiology, diagnostic hemodynamics, and interventional cardiology.

Without openly saying so, nuclear cardiology would learn from the anatomical diagnoses made by cine coronary angiographies and left ventricular hemodynamic studies.

Radioisotope studies improved their sensitivity and specificity parallel to the advancements made in gamma camera machines, radioisotopes, and knowledge. First came isotopic ventriculography during exertion with Tc99 and thallium-201 studies. Then, isonitrile studies with Tc99 joined the lab armamentarium with permanent markers of myocardial perfusion and left ventricular function.

The highly negative predictive value of a gated-SPECT study implied that there was no significant obstruction of epicardial coronary arteries. Also, it made it unnecessary to conduct any anatomical diagnostic studies with cine coronary angiography. This information was reinforced with prognostic studies of myocardial perfusion that proved that a normal study had such a low annual cardiovascular mortality rate that it could not be improved with any revascularization procedure.

A wrong analysis of that era suggested, at the time, that nuclear cardiology studies would replace cine coronary angiography entirely. However, the synergy between nuclear cardiology and interventional cardiology in the therapeutic decision-making process for the benefit of the patient would become a reality sometime later. Cath labs reduced the number of normal studies conducted and dedicated more time and resources to therapeutic procedures that were on the rise: bare metal stents, then drug-eluting stents, experience, and good results in the management of multivessel disease, and left main coronary artery disease.

The synergy between nuclear and interventional cardiology consolidated regarding the therapeutic decision-making process to the point that it came to define revascularization or optimal medical therapy. However, early studies of the pathophysiology of the so-called elastic recoil1,2 broadened our knowledge of restenosis too. Also, nuclear studies allowed accurate definitions of the concept of “complete functional revascularization”.

At the end of the 1980s our publications started reporting on the presence of myocardial ischemia in patients without significant obstructive coronary artery disease that, at the beginning, were interpreted as false positives.

Before knowledge on the action of nitric oxide and the concept of endothelial dysfunction became popular our group published reports on ice tests that tested positive for ischemia in patients with normal exercise myocardial perfusion studies. This lack of coincidence made us diagnose ischemia as a transient process very much like coronary spasm.3,4

Further studies with more in-depth knowledge on microvascular disease and endothelial dysfunction, and the possibility of measuring CFR allowed us to diagnose microvascular disease without obstructive epicardial coronary artery disease, thus contributing to the diagnosis and treatment of patients with angina and angiographically normal coronary arteries that we call today INOCA and MINOCA.5,6

Currently, new challenges arise in the field of cardiology: disease progression in patients with cardiovascular disease has stagnated. Currently, multifactorial etiology has been confirmed: increased obesity with the corresponding metabolic syndrome, insulin-resistance, and diabetes.

The impact of microvascular disease has been underestimated to this date. However, the need for new approaches for the management of ischemic heart disease is unquestionable.

Traditionally, studies define cardiovascular disease in its late or complex stages (obstructive epicardial lesions, myocardial infarction, sudden death). Even to this date, the most important epidemiologic study is still Framingham Heart Study conducted back in 1948.

In 2003 a paradigm shift was proposed aimed at acting early on the prevention and reversal not of the plaque but endothelial dysfunction itself.

Until 2003, prevention had been designed on epidemiological databases by detecting coronary risk factors and assessing the overall risk of each patient. However, with evidence from research studies on endothelial dysfunction and the clinical evidence on the interventions performed with statis, it has become necessary to treat high-risk primary prevention patients “aggressively”.

Both the Danish and the U.S. registries show a significant increase of myocardial ischemia without coronary artery obstruction. Today more than ever the heart team needs to create synergies with the information coming from nuclear cardiology, hemodynamic, and interventional cardiology studies.

The current classification of myocardial ischemia with clinical implications in the right selection of treatment tells us that coronary artery disease should be identified as focal, diffuse, microvascular, or combined. In the anatomical and functionally focal category that studies CFR, interventional cardiology should have better immediate and long-term results. In the combined category, the right selection of the culprit artery and the optimal medical therapy to treat microvascular disease should lead to better results. In the diffuse and microvascular categories, management with individual optimal medical therapy should be the predominant one. Currently, we can not only study the presence of microvascular disease in coronary territories, but also thanks to nuclear and interventional cardiology we can differentiate whether such dysfunction is endothelial-dependent or not, which gives us the possibility of targeting drug therapy based on the physiopathological mechanism involved.

Maybe that lack of differentiation makes the ISCHEMIA trial historic. Nonetheless, its findings are still controversial.

The ISCHEMIA is a study on the management of patients with stable coronary artery disease, and not on revascularization vs no revascularization. Aside from the multiple objections that can be made regarding some criteria used, the ISCHEMIA trial should be interpreted with caution and much detail. An overall conclusion that brings results to a global level would be a flat-out mistake precisely because it does not distinguish patients with focal disease from those with greater microvascular compromise.

In conclusion, coronary artery disease has changed its presentation. The exclusive focal disease we knew decades ago has become less prevalent, and now focal and diffuse disease combined have become a common finding.

Information on microvascular dysfunction has now been added to the mix to coexist with all ways of presentation of coronary artery disease and with prognostic implications regarding the therapeutic decision-making process. The epidemic of obesity, diabetes, and metabolic syndrome plays a fundamental role in this paradigm shift.

Our current challenge is to achieve—through teamwork—a synergy between the functional study of nuclear cardiology and the therapeutic procedures of interventional cardiology to reduce the rates of mortality associated with ischemic heart disease.

Néstor A. Pérez Baliño
Former President of the Argentine Society of Cardiology and the Argentine Foundation of Cardiology.
Head of the Department of Medicine and Nuclear Cardiology at ICBA

Laura E. Grynberg
Department of Nuclear Medicine at Clínica Las Condes, Santiago de Chile.
Former Head of the Department of Nuclear Medicine at Hospital Cosme Argerich,and PET image Consultor at Centro de Imágenes Médicas, Buenos Aires, Argentina

1. Rodríguez A, Santaera O, Larribau M, et al. Coronary stenting decreases restenosis in lesions with early loss in luminal diameter 24 hours after successful PTCA. Circulation1995;91:1397–402

2. Rodríguez A, Santaera O, Larribau M, Sosa MI, Palacios IF. Early decreasein minimal luminal diameter after successful percutaneous transluminalcoronary angioplasty predicts late restenosis. Am J Cardiol1993;71:1391–5.

3. Perez Baliño N, Sosa Liprandi A, Masoli O, Susana Molteni, Teresa Rizzo, Garrido M, Sporn V.Usefulness of radionuclide ventriculography in assessment of coronary artery spasm.The American Journal of cardiology 59 (6), 552-558, 1987.

4. Traverso S, Redruello M, Grynberg L, Cragnolino D, Maciel N, Meretta A, Masoli O, Pérez Baliño N. Perfusión miocárdica SPECT con prueba de frío como predictor de desarrollo de isquemiade esfuerzo en el seguimiento de pacientes asintomáticos con riesgo cardiovascularmoderado. Rev. argent. cardiol. v.75 n.4 Buenos Aires jul./ago. 2007

5. Perez Balino N,Masoli O, Traverso S, Grynberg L, Rappallo C, Redruello M, Rosa D, Cragnolino D, Meretta A, Vidal, L.Cold pressor testing 99Tc MIBI-SPECT useful detecting abnormal coronary vasoreactivity in asymptomatic population with moderate risk of cardiovascular events. PARADIGMA multicenter study. 2005. Journal of Nuclear Cardiology, 12(2):S41.

6. Gobbo M, Meretta A, Sciancalepore M, Retamozo E, Beber E, Rosa D, Perez Baliño N,Masoli O.INOCA: Evaluación no invasiva de los mecanismos fisiopatológicos mediante CZT-SPECT. Rev Argent Cardiol2022;90:194-202.

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