Exercise SE

There are two main types of exercise SE: isometric exercises (e.g., handgrip exercises) and isotonic exercises (e.g., treadmill and ergometer exercises). Exercise SE is preferred for its dynamic evaluation under physiological stress conditions.

• a)

  Treadmill exercise echocardiography:

  • Methods: The workload is incrementally increased using protocols such as the Bruce protocol. ECG and blood pressure are monitored, and echocardiograms are recorded immediately after exercise.

  • Image acquisition: Efficient imaging is crucial, requiring patient cooperation to hold their breath and breathe shallowly post-exercise to improve image quality.

• b)

  Supine ergometer exercise echocardiography:

  • Methods: Patients exercise on a bicycle in a semi-sitting position, with workload increased progressively. ECG and blood pressure are continuously monitored.

  • Precautions: Similar to treadmill echocardiography, images should be acquired during exhalation for optimal image quality.

• c)

  Handgrip SE:

  • This isometric exercise involves sustained handgrip to increase pressure load on the left ventricle (LV) without significantly increasing heart rate.

• d)

  Six-minute walk test:

  • This test involves walking as far as possible in six minutes, with an echocardiographic assessment performed post-exercise to evaluate cardiac function [13].

Interpreting SE requires expertise in evaluating regional wall motion under stress. The wall motion score index is often used to quantify the extent of ischemia, with higher scores indicating more severe diseases. Advanced techniques like Doppler tissue imaging and strain rate imaging can enhance sensitivity in detecting myocardial ischemia, although these are not yet widely adopted in clinical practice [13]. SE assesses IHD using exercise (treadmill or bicycle) or pharmacological method. It has applications even in pediatric populations and offers excellent feasibility with modern technology and contrast agents. It is used to diagnose IHD, assess myocardial viability, and evaluate prognosis. Advances like strain imaging, myocardial perfusion, and 3D imaging continue to enhance its role in cardiac imaging and stress testing [14].

Exercise SE is contraindicated in patients with ACS, poorly controlled heart or respiratory failure, severe hypertension, severe aortic stenosis, severe obstructive hypertrophic cardiomyopathy, fatal arrhythmias, acute aortic dissection, inability to exercise, and lack of patient consent. SE has limitations, including the subjective nature of image interpretation, potential underestimation of multi-vessel disease, and challenges in patients with obesity or lung disease. Test sensitivity depends on the level of stress achieved, with lower sensitivity under suboptimal stress [15].

Exercise SE is generally safe, with low incidences of severe complications such as arrhythmias or myocardial infarctions (MIs). However, the presence of emergency equipment and monitoring systems is essential.

Dipyridamole SE

The dipyridamole test [16] plays a critical role in the evaluation of IHD by leveraging its vasodilatory properties to induce hyperemia and, in certain conditions, ischemia. The outcome of the test largely depends on the dose of dipyridamole and the patient’s coronary anatomy. Low doses typically highlight the hyperemic effect in patients with no to moderate CAD whereas higher doses induce ischemia, particularly in those with moderate to severe CAD.

Dipyridamole works by increasing endogenous adenosine levels, which in turn activate A2A receptors, leading to vasodilation. This mechanism is particularly useful for identifying ischemic areas through induced flow maldistribution, known as the “steal” phenomenon. This phenomenon can be vertical (between subepicardial and subendocardial layers) or horizontal (between different vascular beds).

The test starts with an intravenous dipyridamole infusion, followed by echocardiography to assess wall motion and coronary flow reserve (CFR). High doses (up to 0.84 mg/kg) and accelerated protocols have improved sensitivity, especially in detecting minor CADs and in patients on antianginal therapy.

Dipyridamole SE offers high diagnostic accuracy, comparable to dobutamine SE (DSE) with high-dose protocols. The test is generally well-tolerated, with minor side effects resolving with aminophylline.

Furthermore, it allows for simultaneous assessment of myocardial function and coronary flow, providing comprehensive diagnostic and prognostic information. It is suitable for various patient groups, including those with microvascular dysfunction and conditions like left bundle branch block or non-obstructive CAD.

The ABCDE protocol enhances the prognostic value of dipyridamole SE by assessing multiple cardiac functions. Overall, dipyridamole SE is a robust, versatile, and safer choice for evaluating IHD, especially in specific patient populations and settings with limited resources.

Low-dose dipyridamole: At lower doses, particularly in patients with absent to moderate CAD, the hyperemic (vasodilation) effect of dipyridamole is predominant. This means that increased blood flow is achieved without significant ischemia.

High-dose dipyridamole: In cases of moderate-to-severe CAD, higher doses of dipyridamole tend to produce an ischemic response. The drug induces myocardial ischemia by causing a steal phenomenon, where blood is redirected away from areas supplied by stenotic arteries.

Echocardiography imaging detects ischemia by observing wall motion abnormalities. A positive test shows areas of the heart muscle that do not contract normally under stress, indicating compromised blood flow.

The typical protocol involves an initial low dose of dipyridamole followed by higher doses or co-administration with atropine to enhance sensitivity.

CFR is an important measure obtained during dipyridamole stress testing. A normal CFR (≥ 2.0) indicates adequate coronary blood flow reserve, while a reduced CFR suggests significant epicardial or microvascular disease.

Measurements of diastolic flow velocity in the left anterior descending artery are often used for this purpose.

Vertical steal: Blood is diverted from the subendocardial to the subepicardial layers, particularly in single-vessel disease.

Horizontal steal: Occurs in multi-vessel disease or chronic occlusions with collateral circulation, where blood flow is diverted from ischemic regions due to the vasodilation of vessels supplying collateral flow.

Diagnostic accuracy: High-dose dipyridamole echocardiography is highly accurate for detecting CAD, with sensitivity and specificity comparable to other stress tests like DSE.

Safety profile: Dipyridamole is generally well-tolerated, with minor side effects such as headache and flushing. Major complications are rare.

Dipyridamole SE provides significant prognostic information in various patient subsets, including those with chronic CAD, recent MI, and those undergoing non-cardiac surgery.

Patients with severe carotid disease, second or third-degree atrioventricular (AV) block without a pacemaker, or bronchial asthma should avoid dipyridamole.

Withdrawal of theophylline or caffeine is required before testing to ensure adenosine receptor availability.

The use of advanced imaging technologies, such as coronary flow velocity imaging allows for the simultaneous assessment of coronary flow and myocardial function, improving diagnostic accuracy and patient management.

In summary, dipyridamole stress testing, particularly when combined with echocardiography, is a valuable tool in the diagnosis and management of IHD. It allows for the assessment of both CFR and myocardial ischemia, offering critical information for patient care and prognostication.

DSE

DSE [17] is effective for diagnosing IHD (Figure 2). However, side effects can limit achieving maximal pharmacological stress in about 10% of patients. Common side effects include complex ventricular tachyarrhythmias, hypotension, bradycardia, and supraventricular tachyarrhythmias. Despite these potential issues, side effects usually subside after stopping the drug, given dobutamine’s short half-life. Major complications are rare, occurring in approximately 1 out of 300–350 cases. It’s crucial to have proper resuscitation facilities and experienced personnel present during the test.

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Figure 2. 

Pharmacological stress echocardiography with dobutamine, apical two-chamber views

DSE is highly accurate for detecting CAD, with a sensitivity and specificity of 81% and 84%, respectively. It is comparable to other stress testing methods like exercise echocardiography and stress scintigraphy. DSE is also effective for assessing myocardial viability, differentiating between viable myocardium and scar tissue, and predicting functional recovery post-revascularization.

Dobutamine can occasionally induce coronary vasospasm, which needs to be recognized due to its clinical implications. Vasospasm can enhance DSE sensitivity but also cause false positives. It can occur during dobutamine infusion or after beta-blocker administration. Recognizing and treating coronary vasospasm appropriately, such as with nitrates instead of beta-blockers, is crucial to avoid adverse outcomes.

DSE has excellent prognostic value, comparable to other stress tests. The comprehensive assessment of regional wall motion, left ventricular contractile reserve, coronary flow velocity reserve, and heart rate reserve during DSE adds incremental prognostic value, making it a robust tool for evaluating IHD.

DSE’s limitations include side effects in 5–10% of tests and challenges in echocardiographic interpretation at high heart rates. Specific contraindications include severe arterial hypertension, uncontrolled tachycardia, hypertrophic cardiomyopathy, and recent MI. Utilizing ultrasound-enhancing agents can improve accuracy when visualizing endocardial borders is difficult.

DSE is considered a key diagnostic tool for IHD. It is also used for evaluating myocardial viability, assessing valvular heart diseases, and in heart transplant recipients to detect cardiac allograft vasculopathy. The method is validated and recommended by major cardiology guidelines for various clinical settings.

Overall, while DSE carries risks, its benefits in diagnosing and managing IHD are significant, provided it is performed under controlled and well-monitored conditions.

SE is a versatile and effective tool for diagnosing and managing CAD. Its ability to provide diagnostic and prognostic information at a relatively low cost and no radiation exposure makes it a preferred choice in many clinical scenarios. Continued technological advancements are likely to enhance its accuracy and expand its role in cardiovascular care. Several recent studies underscore the diagnostic value of strain measurements in assessing CAD and MI [18–21]. The global circumferential strain (GCS) and the ratio of GCS to global longitudinal strain (GLS) were significantly reduced in patients with CAD, particularly those with more extensive disease, indicating that GCS can serve as an effective supplementary diagnostic tool when traditional methods are inconclusive [20]. However, limitations such as small sample sizes and a lack of long-term follow-up raise concerns about the generalizability of these findings [18].

Other studies have highlighted that GLS at rest was less negative in CAD patients, with substantial overlap with non-CAD patients, which reduces its specificity [21]. The incorporation of stress testing, such as dobutamine echocardiography, has shown potential for enhancing diagnostic accuracy, emphasizing the need for standardized strain measurement techniques. Additionally, some research indicates that 3D GCS offers superior accuracy in diagnosing large MIs compared to traditional two-dimensional methods. This aligns with evidence suggesting that both GLS and transverse longitudinal strain (TLS) are strong predictors of myocardial non-viability in patients experiencing cardiogenic shock [19].

While strain measurements, particularly GCS and 3D GCS, show considerable promise for diagnosing CAD and assessing the severity of MI, these studies reveal a need for improved standardization, larger sample sizes, and long-term follow-up. Addressing these gaps could enhance diagnostic accuracy and ultimately improve patient outcomes in cardiovascular care.

Identification of IHD via scintigraphy

IHD is typically identified using myocardial perfusion imaging (MPI), which can be part of a nuclear stress test or involve pharmacologic stress. A positive result indicates insufficient blood flow to the heart, which may only become apparent during the exercise phase of the stress test. Positron emission tomography (PET) plays a key role here by detecting photons emitted from injected radiolabeled tracers with a PET scanner.

• PET MPI

PET acquires dynamic rest and stress images to quantify myocardial blood flow and flow reserve. This imaging technique provides both qualitative and quantitative assessments. By comparing stress and rest images, PET can identify perfusion defects, describe affected segments, assess defect severity, and determine the extent of LV involvement.

• Single-photon emission CT MPI

Single-photon emission CT (SPECT) is another method used in MPI. It detects gamma rays emitted by radionuclides such as 201Tl and ^99mTc-sestamibi (Figure 3). By comparing ECG-gated stress and rest images, SPECT helps in identifying perfusion defects. Although SPECT is widely available and has well-established protocols, it has limitations, including lower spatial resolution compared to PET.

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Figure 3. 

Myocardial perfusion tomography with ^99mTc-sestamibi

Hibernating myocardium

Hibernating myocardium is a state of chronic ischemia that may recover after revascularization. PET is valuable in this context as it produces metabolic images that, when compared to perfusion images, help identify hibernating myocardium. Metabolic tracers such as fluorine-18 (18F) fluorodeoxyglucose and carbon-11 (11C) acetate are used. If a matched defect is observed on PET perfusion images along with metabolic activity, indicates viable myocardium.

Indications and contraindications [22, 24]:

Indications:

• Known or suspected stable angina;

• Assessment of the physiological significance of known coronary artery stenosis.

Contraindications:

• Unstable angina or acute MI;

• Decompensated heart failure;

• Acute illnesses like acute pulmonary embolism, acute myocarditis and/or pericarditis, aortic dissection, or acute cerebrovascular accident;

• Severe pulmonary hypertension;

• Critical left ventricular outflow obstruction or critical aortic stenosis;

• Uncontrolled severe hypertension (> 200/110 mmHg);

• Uncontrolled arrhythmias, including atrial fibrillation with rapid ventricular response, ventricular tachycardia, and second- or third-degree heart block without a functioning pacemaker.

Modality or vasodilator-specific contraindications:

• Asthma or emphysema with active wheezing (for adenosine, dipyridamole, regadenoson);

• Resting systolic blood pressure < 90 mmHg (for adenosine, dipyridamole, regadenoson);

• Typical contraindications for magnetic resonance imaging (MRI);

• Renal insufficiency [estimated glomerular filtration rate (GFR) < 30 mL/min per 1.73 m² for MRI and CT contrast];

• Known hypersensitivity to the contrast material or vasodilator agent being considered;

• History of asthma or emphysema (for adenosine, dipyridamole); supplies for respiratory emergencies should be available if using regadenoson;

• Caffeine intake within the last 12 hours.

Warnings or other relative contraindications:

• Hypertrophic cardiomyopathy with severe left ventricular outflow tract obstruction;

• Significant arrhythmias; heart rate > 100 beats per minute that cannot be controlled with β-blockers;

• Moderate renal insufficiency (GFR 30–60 mL/min/body surface area);

• Morbid obesity (body mass index > 40);

• Recent seizure or stroke;

• Electrolyte level abnormalities.

Procedure

Beta-blockers or ivabradine are used to lower the heart rate to below 60 beats per minute to reduce motion artifacts during the scan.

During the imaging session, a CT scanner, ideally with at least 64 slices-captures detailed images of the coronary arteries. A non-contrast scan first measures the Agatston score to evaluate coronary calcification. Following this, a contrast agent is injected into the bloodstream to enhance visualization of the arteries. The scan is synchronized with the ECG to capture images during minimal heart motion.

The resulting images are reconstructed into a three-dimensional model of the coronary arteries. Cardiologists analyze the images to assess vessel narrowing and identify any significant stenosis.

Advantages

One of the primary advantages of CCTA is its ability to accurately exclude the presence of CAD in symptomatic patients. A normal CCTA result is associated with a good prognosis and may eliminate further invasive testing. This aspect contributes significantly to streamlined patient management and reduces the frequency of unnecessary procedures.

CCTA is also valuable in identifying non-obstructive CAD, which allows for early intervention and preventive therapy that might be overlooked by other non-invasive tests. Early identification improves cardiovascular risk management and enables timely treatments.

While CCTA may increase the total number of catheterizations, it reduces unnecessary invasive procedures by accurately identifying patients with non-obstructive CAD. This precise identification ensures that resources are focused on patients who genuinely need invasive testing.

Moreover, CCTA has been associated with increased rates of revascularization and a reduction in MIs. By identifying significant lesions that require intervention, it facilitates more effective treatment and improved patient outcomes.

The integration of CCTA with FFR-CT further enhances diagnostic accuracy by evaluating the functional significance of coronary lesions. FFR-CT provides a high level of accuracy in assessing the physiological impact of stenosis, which guides treatment decisions more effectively.

Risks

Despite its advantages, CCTA presents certain risks. One notable risk is radiation exposure, which, while minimized by advancements in technology and imaging protocols, remains a concern. The potential long-term effects of ionizing radiation must be considered, and efforts must be made to apply the lowest effective dose.

Contrast agents can cause allergic reactions or adverse effects. While such reactions are rare, they require careful monitoring and management during the procedure.

Additionally, CCTA primarily provides anatomical information and does not directly assess the functional significance of coronary lesions. This limitation can lead to discrepancies between the anatomical findings and their functional implications. To address this, FFR-CT can be used in conjunction to provide a more comprehensive evaluation of stenosis.

Image quality can be affected by factors such as severe coronary calcification, high heart rates, or patient motion, which can impact diagnostic accuracy. In cases where image quality is compromised, additional testing or the use of FFR-CT may be necessary to achieve a complete assessment.

Lastly, CCTA can sometimes lead to overdiagnosis or false positives, where non-significant lesions are incorrectly identified as significant. This can result in unnecessary follow-up tests or interventions, emphasizing the need for careful interpretation and management.

FFR-CT: FFR-CT provides a non-invasive approach for assessing the functional significance of coronary stenosis, integrating both anatomical and physiological data from coronary CT angiography. This helps clinicians determine whether a stenosis is hemodynamically significant, which is a key factor in deciding the need for interventions such as coronary revascularization.

One advantage of FFR-CT over traditional CT alone is its ability to offer more detailed insight into blood flow and pressure differences across a coronary lesion, enabling more personalized decision-making. However, its limitations include the need for high-quality imaging data and computational resources, as well as a time delay for analysis, since the data often have to be sent to specialized centers for interpretation.

FFR-CT has high sensitivity for significant stenosis, but its lower specificity can cause false positives, leading to unnecessary invasive procedures. As a result, FFR-CT is increasingly seen as a complementary tool that helps reduce the number of unnecessary catheterizations but should be integrated with clinical judgment and possibly other non-invasive tests like SE or MPI to improve overall diagnostic accuracy. It offers high negative predictive value and sensitivity but has moderate positive predictive value (60–70%). A value ≤ 0.80 indicates significant stenosis and typically leads to coronary angiography, while values > 0.80 suggest follow-up or stress testing. FFR-CT combines anatomical and physiological data, improving diagnostic accuracy but requiring high-quality imaging and advanced analysis.

Ongoing advances, including AI and machine learning, are expected to further refine FFR-CT analysis, making it faster and more accurate, and potentially improving its positive predictive value in the future [28].