T he exercise test has for decades been an unavoidable non-invasive method in the diagnosis of coronary artery disease (CAD). Despite the development of other modern and sophisticated non-invasive and invasive methods for CAD diagnosis, the exercise test has not lost its place to this day and is usually the first step in the diagnosis of stable CAD, monitoring and evaluation of potential residual ischemia in coronary patients after a previous infarction, percutaneous interventions, and/or surgical myocardial revascularization and the objectivization of the functional capacity of individual patients. The advantage of the stress test is that it is a widely accessible, simple to perform, and reliable method especially in relation to the safety of the tested patients. The estimated specificity (ability to recognize normal subjects) of the exercise test is 85-90%, and the sensitivity (ability to discover coronary disease) is 60-70% (1-3).

Historically, the beginnings of the development of modern exercise testing reach about a hundred years into the past. Already in 1918, Bousfield published a paper in the Lancet journal describing changes in the electrocardiogram (ECG) of a coronary patients with an anginous pain attack demonstrated as a denivelation of the ST-segment in three standard ECG leads (2, 4). In 1928, Feil and Siegel (2, 5) also described changes in ST-segment and T-wave in patients with known angina pectoris after exposure to physical activity (repeatedly sitting and standing up) as well as the presence of chest pain and its regression after cessation of the activity or the administration of nitroglycerine medication. Master and Oppenheimer (2, 6) were probably the first to describe an exercise test in 1929, but they only monitored changes in blood pressure and heart frequency, not yet fully recognizing the potential value of ECG in the detection of ischemia. Twelve years later, Master and Jaffe (7) demonstrated the usefulness of analyzing ECG changes before and after exertion for the detection of myocardial ischemia. In 1931, Wood and Wolferth (2, 8) also described ECG changes associated with ischemia caused by exertion and stressed the usefulness of exposure to physical exertion in the detection of ischemia, while also noting that such tests are too dangerous to perform in patients with diagnosed CAD.

The predecessor for the later development of modern ergometric protocols was Master’s simple “two-step” test and the establishment of Master’s ECG criteria in the detection of myocardial ischemia (9). The basics of modern exercise testing were laid down during the 1950s, when Bruce (10) described the treadmill exercise test. Today, the different protocols for treadmill testing are developed and based on the principles set by Bruce in 1956 (10). In addition to the modified Bruce protocol, it is important to mention the symptom-limited, submaximal Naught protocol, which has in practice shown itself to be equally valuable in the detection of ischemic changes in coronary patients (11).

Olaf Astrand and Irma Rhyming created a nomogram for determining the maximum aerobic capacity in the step test (12) in 1954 and one for the bicycle test in 1960, which is widely applied in sports medicine and testing of patients (13).

By 1969, numerous papers were published on the use of computers in analyzing ST-T segment oscillations (14). Soon after, several reports were published on the correlation of detected ischemic ECG changes in exercise tests with the results of coronary angiography (15, 16).

According to available data (17-25), the first reports related to the development and standardization of exercise tests for cardiologic patients in Croatia date from the end of the 1960s (17, 18) (Figure 1A and 1B). During this period, a team of doctors in the Thalassotherapia Cardiological Rehabilitation Center in Opatija under the leadership of the physiologist Prof. Krunoslav Turkulin intensively worked on the standardization and implementation of a diagnostic method that was innovative at the time not only in Croatia but in the whole region. The document “Ergometrija u kardiologiji i pulmologiji” (Ergometry in cardiology and pulmology) published in 1971 (19) (Figure 2A and 2B), which was preceded by a meeting of experts organized by the Yugoslavian Cardiologic Society held in Opatija, was the first to describe the required technical gear, types of tests and exertions, test conditions, indications and contraindications for testing, ECG changes, and the clinical application of the exercise test. In the foreword of this document, the current director of the Thalassotherapia in Opatija and the president of the Yugoslavian Cardiologic Society, Prof. Čedomil Plavišić, stated that “the development of technology, electronics, and automation have led to deep-rooted changes in clinical medicine as whole – especially in the field of diagnostics. Even with the knowledge that proper evaluation is the basis of all treatment and rehabilitation, the methods have not yet been standardized, especially in issues of terminology, device choices, methods, and consistent interpretation of results”. Three years later, the integral text (19) was republished in an abbreviated version due to the interest shown by physicians in the field, and the “earlier publication was sold-out” (20).

Furthermore, since 1971 a group of scientists from the Faculty of Electrical Engineering in Ljubljana and the physicians from the Thalassotherapia in Opatija started developing a program for computer analysis of ECG during exertion with the goal of improving the analysis of ischemic ECG changes and reducing its limitations (21, 22). Prof. Dr. Turkulin received the Kidrič award in 1982 for this research (an award of the highest level for achievements in the field of science, awarded between 1957-1991 in Slovenia). The Gorenje company later build a computer (MAE101) for the analysis of ECG during exertion based on the results of that project and research.

Based on their extensive experience in rehabilitation and functional exercise testing in cardiac patients, a group of authors created the “medical criteria for determining the physical damage in heart patients” in 1980, where the main determinant was exercise testing of cardiac patients (25).

In 1985, Prof. Dr. Krunoslav Turkulin from Opatija became the head of the Cardiology Department at the Special Hospital for Medical Rehabilitation in Krapinske Toplice, where he worked until his retirement in 1997. Prof. Dr. Turkulin significantly improved the work of the Cardiological Rehabilitation Department in Krapinske Toplice over the following years, introducing new modalities of physical training, new diagnostic techniques, and improvements in research and education. During those years, the hospital became an important center for non-invasive cardiovascular diagnostics and exercise testing in particular.

In conclusion, although exercise testing in widely and routinely applied today, it has, like most new diagnostic and treatment methods, gone through its own “thorny” path towards full affirmation in clinical practice. According to Dr. Turkulin himself, at the start of the development and wider application of exercise testing in Croatia and more intensive training for coronary patients was faced with suspicion, unvoiced skepticism, and resistance from individual peers at the time who clearly held the position that “this can seriously harm patients”. Fortunately, these times are behind us, and this method is now routinely applied in clinical practice and holds an irreplaceable position in the diagnosis and evaluation of coronary disease, which is one of the leading causes of illness and mortality in the modern world.