Diagnosis Of Coronary Heart Disease

The higher incidence of CAD with escalating costs of treatment emphasizes the need of early screening and prevention. Therefore, the objective for the future would be, not only to identify high-risk individuals for CAD, but also to identify disease in the asymptomatic, low- and intermediate-risk groups. This would allow defining management strategies with expectation to reduce future coronary ischaemic events.

The initial diagnosis of coronary heart disease can be established on initial clinical evaluation by the cardiologists. However, in atypical cases confirmatory tests are required. Similarly, tests are also important for the management decisions. The assessment of risk factors is helpful to define pre-test likelihood of CAD. An ideal screening methodology should be capable of not only detecting early obstruction or abnormal coronary flow, but also predict future cardiac events. The use of coronary angiography has demonstrated improved outcomes. However, due to its invasive nature and higher costs, it cannot be used as a screening or early diagnostic tool.
The various non-invasive tests used are enlisted below briefly:

Exercise Stress Testing

The exercise ECG stress test is the most widely non-invasive method used for clinical evaluation of CAD. There are two major methods of exercise stress testing, (i.e. dynamic exercise and pharmacological stress), and can be used alone or in combination with myocardial perfusion imaging, echocardiograpy and MRI. Other methodologies including isometric handgrip exercise stress test; atrial pacing simulation, cold pressor and mental stress tests are less feasible in clinical routine.

a) Dynamic (Physical) Stress Test
Physical exercise is a physiological stress test. It not only provokes perfusion and ventricular function abnormalities, but also provides crucial clinical information regarding symptoms, exercise capacity, and haemodynamic parameters, helping diagnostic and prognostic assessment. The bicycle (ergometer) or treadmill exercise are two standard techniques, involving either symptom-limited exercise testing to elicit symptoms and / or haemodynamic / electrocardiographic changes. During the stress test, the double product (HR x Systolic BP) reflects myocardial oxygen demand and ideally should be greater than 20,000 or at least double the patient’s resting value. An adequate stress test is imperative for reliable results. A heart rate less than 85% of the maximal target heart rate in asymptomatic patients leads to sub-optimal results.

b) Pharmacological Stress Test
Pharmacological stress test is carried normally out in patients unable to exercise . The pharmacological stress agents are categorized into two sub-groups.

i)  Vasodilators: Adenosine, Dipyridamole
ii) Inotropes: Dobutamine

i) Vasodilators
The degree of coronary hyperaemia attained with coronary vasodilators, exceeds that achieved by dynamic exercise, achieving a similar diagnostic accuracy to that of dynamic exercise.

Adenosine:  Physiological vasodilator
Adenosine is a naturally occurring purine, present in the body as a result of dephosphorylation of adenosine monophosphate (AMP) and intracellular degradation of S-adenosyl-homocysteine (SAH). Adenosine is rapidly taken-up into erythrocytes and vascular endothelium from blood and is either converted into adenosine triphosphate or metabolised into uric acid. The effect of Adenosine is primarily through its effect on Adenosine receptors, causing vascular smooth muscle cell relaxation with coronary  (increased flow) and systemic vasodilatation (decreased BP). The effect on coronary vasodilatation is required for perfusion imaging.

The most common side effects are flushing, shortness of breath, gastrointestinal discomfort and mild non-specific chest pressure, with occasional (2-5%) AV block . Due to a short half-life, discontinuation of the infusion immediately resolves most side effects. It should not be used if there is evidence or suspicion of SA node disease .

Dipyridamole
Dipyridamole blocks cellular uptake of endogenous adenosine, causing an indirect but variable degree of coronary vasodilatation. An adequate pharmacological effect can be judged by an increase in HR by more than 10 beat per minute (bpm), a decrease in diastolic blood pressure and symptomatology.

Dipyridamole and Adenosine are contraindicated in patients with a second or higher degree atrioventricular block .  It should be used with caution in cases of first-degree block, as it may progress to a higher degree of block, particularly with dipyridamole due to its longer half-life.
It should be recognised that the chest pain associated with vasodilators is not specific for myocardial ischemia. Normally the patients with angina-like pain and normal coronary angiograms have a low pain threshold and reduced tolerance to pain induced by adenosine.

Simultaneous Coupling of Vasodilator and Dynamic Stress Tests:
The coupling of dipyridamole or adenosine infusions with dynamic stress is safe. Most of the initial studies implemented a low level of dynamic exercise (89), while only a few later studies used higher levels of exercise. The main advantages of adding physical stress to vasodilator pharmacological stress are reduction in adverse effects and improved image quality. Adenosine combined with exercise also predicts a higher number of coronary events than adenosine infusion alone (3.91% vs. 3.20%).

ii) Inotropes
Dobutamine is a sympathomimetic agent and has been widely used as a stress agent not only in myocardial perfusion imaging, but also for echocardiography and MRI. Dobutamine, through its effect on the beta-1 receptors, increases heart rate and myocardial contractility; augmenting cardiac output, while its direct effect on coronary arterioles causes mild coronary dilation. Dobutamine stress myocardial perfusion imaging has overall sensitivity, specificity, and accuracy of 88%, 74%, and 84%, respectively, for CAD.

The use of Dobutamine in myocardial perfusion imaging, echocardiography and MR imaging is usually selective being limited to patients with contraindications to dipyridamole and adenosine. It should not be used in cases of bundle branch block, significant hypertension or hypotension, other types of significant arrhythmias, and aortic stenosis.
Dobutamine infusion is commonly started at 10 mg/kg/min, with gradual increments at 3-minute intervals,  The commonest reported side effects of Dobutamine are chest pain, palpitations, headache, flushing, and dyspnoea.

Coronary CT

Calcium Scoring and CT Angiography

Coronary calcium scoring using electron-beam and multi-slice CT scanners has been employed for detection and prognosis of Coronary artery disease. Patients with calcium score of more than 400 have been categorized very high risk, while less than 100 are implicated with low-risk. However, myocardial perfusion abnormalities have been observed in approximately 9% patients with coronary calcium scores of ranging between 1 - 10, and 20% with scores of 11 to 100 (136). 

With recent advancement in technology, Coronary CT angiography (CTA) has become a non-invasive alternative for imaging the coronary arteries in an increasing number of patients, and may obviates need of invasive angiography in many patients. The recent generation of multi-slice scanners with newer techniques have dramatically reduced radiation exposure to the patients. Unlike coronary artery calcium scoring, which utilizes non-contrast CT to assess atherosclerotic disease burden, CTA allows direct visualization of the coronary artery wall and lumen with the administration of intravenous contrast. The degree of coronary luminal stenosis can be reliably estimated, as can the presence or absence of both calcified and non-calcified plaques. Sensitivities and specificities of more than 90%, and negative predictive values of up to 100% for the exclusion of obstructive coronary artery disease (CAD) for both native arteries as well as bypass grafts have been reported using this technique.  CTA may also be helpful in low- and intermediate-risk patients with subacute or chronic chest pain syndromes. The use of CTA as a screening test for detecting coronary artery disease in asymptomatic patients with traditional risk factors is controversial, and has not been widely recommended. Currently, the detection of CAD (both obstructive and non-obstructive) by CTA in asymptomatic patients raises several questions:

		Does the presence of mild non-obstructive CAD in an otherwise healthy individual warrant immediate and life-long treatment with a statin?
		Will treatment with a statin alter the natural progression of coronary disease found on screening CCTA?
		Does the finding of “clean” coronaries on CTA in a patient with traditional risk factors reduce the urgency for aggressive lifestyle modification and medication therapy?

Further studies are needed to provide guidance with regards to these matters. The radiographic finding of coronary artery disease may have a psychological impact on the patient that may facilitate lifestyle modification and medication compliance. Similarly,   it may be argued that patients with traditional risk factors ought to undergo aggressive risk factor modification without the need for CTA.

Echocardiography

Stress Echocardiography is a useful non-invasive method to predict areas of viable myocardium, which would benefit from further interventional procedures like Angioplasty or Bypass Surgery. Myocardial Contrast Echocardiography (MCE) has also revealed comparable results with myocardial perfusion SPECT imaging (133), but such studies are limited.

Cardiac MRI

Magnetic resonance imaging (MRI) is one of the most exciting and challenging imaging techniques for the cardiovascular system. Its established clinical indications include the diagnosis of pericardial disease, aortic disease, cardiac masses, congenital heart disease, anomalous coronary arteries, and right ventricular dysplasia.  However, the indications for cardiovascular MRI are growing as its spatial resolution and versatility is increasingly acknowledged.  CMRI is currently considered the gold standard for quantification of ventricular volumes, function, and mass. Thus, this technique is ideally suited to assess the efficacy of therapeutic interventions on ventricular hypertrophy and remodelling, which may allow a reduction in sample size to show clinically relevant effects. Comprehensive functional assessment is possible by CMRI due to its capability to measure flow velocity and flow volume, which is a basic requirement to quantify lesion severity in valvular heart disease. Over recent years its use in Coronary artery disease has also grown.  Magnetic resonance imaging can be used to assess myocardial perfusion with or without vasodilator stress. Coronary artery imaging for diagnosis of the severity of disease remains in development, as does imaging of coronary flow and flow reserve. Other exciting applications currently being investigated include real-time imaging and intravascular MRI, enabling imaging from the inside of vessels outward, thereby enhancing the ability to image atherosclerotic plaque. The applications of MRI to the cardiovascular system are rapidly expanding and will continue to do so in the coming few years.

Myocardial Perfusion Scintigraph

Myocardial Perfusion SPECT

SPECT of the heart is a well-established nuclear imaging technique, widely used in assessment of coronary artery disease. It involves taking a series of pictures around the chest after injecting a radioactive tracer into the blood. Then computer graphics are used to create images of slices through the heart. This technique has been applied to the heart for myocardial perfusion (blood flow) imaging with agents like thallium-201 and the technetium-based myocardial perfusion tracers. These agents are injected either at rest or with exercise or pharmacologic stress. SPECT has ability to localize coronary artery disease and extent and severity of perfusion abnormalities as well as function, which are very crucial to predict prognosis.

Myocardial Perfusion PET

Positron emission tomography (PET) allows the study and quantification of various aspects of heart function. Clinical studies suggest an important role for PET in diagnosing patients, describing disease and developing treatment strategy. Two areas of clinical application have emerged:

PET is highly accurate for detecting, localizing and describing coronary artery disease that impairs blood flow to the myocardium. This can be performed without an on-site cyclotron, using generator-produced isotopes such as rubidium-82.  The sensitivity and specificity of PET perfusion are higher than SPECT. These advantages translate into fewer inconclusive results. PET also has potential to calculate blood flow in a particular region of the heart.

PET accurately identifies injured but viable myocardium, which would improve after revascularisation. Most commonly isotope used for this type of study is F-18 Fluorodeoxyglucose (FDG).