10-02: Heart Disease: Diagnostic Testing

The chest radiograph provides information about heart size (with cardiomegaly being a poor prognostic sign in chronic heart failure), the pulmonary circulation (with characteristic signs suggesting both pulmonary arterial or pulmonary venous hypertension), primary pulmonary disease, and aortic abnormalities. Individual chamber sizes can be estimated, and the presence of pleural effusions noted. The echocardiogram, though, provides more reliable cardiac information than the chest radiograph about chamber size and hypertrophy, and the presence of pericardial effusions, valvular abnormalities, and congenital abnormalities (VIDEO 10–1). Use of regional stress/strain measures and Doppler flow patterns can also contribute to the assessment of myocardial dysfunction and valvular abnormalities. The ECG indicates cardiac rhythm, reveals conduction abnormalities, and provides evidence of ventricular hypertrophy, MI, or ischemia (eFigures 10–10 and 10–11). ST segment and T wave changes may reflect these processes but are also noted with electrolyte imbalance, medication effects, and many other conditions (eFigure 10–12). Routine radiographs and ECGs, however, are not recommended to screen for heart disease in otherwise asymptomatic patients without any clinical findings to suggest heart disease is present. Stress testing is useful in eliciting ischemia due to fixed coronary lesions, but its use is limited for accurately diagnosing coronary disease in the typical asymptomatic patient. For instance, it is useful to recall Bayes theorem when contemplating stress testing patients as part of an “executive physical.” Bayes theorem notes that the accuracy of the results of a test depend on the risk of disease. If the patient is at low risk for CAD, for instance, one can expect a high number of false-positive stress results. If the patient is at high risk for CAD, one can expect a high number of false-negative results. Stress studies are most effective in those with an intermediate risk for CAD. The clinician’s goal is to help define the CAD risk using the history, physical examination, and other available laboratory tests. The Framingham Risk scoring system and the 10-year atherosclerotic risk calculator (http://my.americanheart.org/cvriskcalculator) can help, and these are readily available as free applications for mobile devices. Stress testing may also be useful in non-CAD patients whenever symptoms seem disproportionate to anatomic defects. For instance, in valvular disease, if the patient is complaining of major symptoms but has only minor anatomic disease, a stress study may help define exercise capacity. The stress may be combined with echocardiography to further assess ventricular function, valvular regurgitation or stenosis or pulmonary pressures. In patients with aortic stenosis, a failure of the BP to increase with stress is used as an indicator of the need for aortic valve replacement or implies high risk in patients with hypertrophic cardiomyopathy. Similarly, if there is significant disease by echocardiography, but few or no symptoms, the stress study may define an unrecognized disability. Stress ECG and pulmonary function testing (cardiopulmonary stress testing) are used together to define maximal cardiac output (VO_2max) with exertion and the slope of the ratio of expiratory ventilation/carbon dioxide release (V̇/V̇CO₂). These tests can help differentiate a pulmonary from a cardiac limitation. They are routinely used to help guide the need for intervention, such as heart transplantation.

Nuclear stress testing provides relative perfusion data following injection of a radioactive material (either technetium or, rarely, thallium) when the heart undergoes stress either by exercise or by injection of a coronary vasodilator. In general, the coronary flow to a coronary bed should augment with exercise or administration of a coronary vasodilator, but the area downstream from a fixed coronary blockage will not increase perfusion as much as the normal bed. The result is a relative “defect” on the perfusion image. The location and severity of the defect(s) can be semi-quantified and scored. The summed scores of the abnormal areas have been found to correlate with prognosis; thus, radionuclide imaging provides information for both ischemia and prognosis in patients with CAD. SPECT (single photon emission computed tomography) provides tomographic slices of the heart for imaging and is a marked improvement over planar imaging methods. Images from the SPECT can be reassembled over time, enabling the wall motion to be imaged and an estimate of the ejection fraction (EF) to be obtained. PET (positron emission tomography) uses short-lived radionuclides that require an on-site cyclotron, but it can provide more quantitative coronary perfusion information and can distinguish viable myocardium from scar tissue more accurately than other nuclear methods. When glucose is tagged (FDG imaging), PET reveals areas of inflammation as well. It is used to help define inflammatory myocarditis or endocarditis when other tests are inconclusive. Radionuclide angiography using Tc-99m tagged red blood cells provides imaging of the heart chambers and is often considered the “gold-standard” for determining the EF, since it simply evaluates attenuation corrected counts in the chamber at end-diastole and end-systole. The EF is simply the stroke counts over the end-diastolic counts. Its use has diminished greatly, though, since more accurate methods (such as MRI) have been developed. MRI provides high-resolution tomographic images of cardiac anatomy and vasculature and can also assess coronary perfusion using pharmacologic vasodilators. The images are dynamic, and valvular stenosis and regurgitation can be quantitated with no patient radiation exposure. Certain characteristics of MRI imaging of the myocardium also help distinguish inflammation, prior MI, or infiltrative processes such as amyloidosis. It is a highly accurate measure of cardiac volumes and function and is particularly better than echocardiography for RV volume measurements. It can provide imaging of the great vessels and a quantitative measure of regurgitation as well. CT angiography scanning has developed to a point where radiation issues are less of a concern, and it also provides high-resolution 3-dimensional images of the aortic vasculature and other heart structures. In addition, the better resolution of CT over MRI provides noninvasive coronary artery assessment. Coronary CT angiography is particularly accurate at identifying a normal coronary circulation. Newer uses of CT now include measures of atrial appendage thrombi and gated studies can provide motion images for RV and LV function. Further improvements are able to provide FFR (functional flow reserve) data. Calcium scoring of the amount of coronary calcium present in the coronaries during CT angiography of the heart has correlated well with the extent of CAD and higher scores have been correlated with an increased risk of future coronary events. Cardiac risk guidelines suggest that a calcium score greater than zero should imply there is some atherosclerosis present, and this is now used to trigger the initiation of a statin in patients with borderline LDL values. Further improvements in CT coronary angiography include methods to measure the flow reserve across identified lesions, and this may become more useful as an alternative to invasive cardiac catheterization and FFR or instantaneous wave-free ratio (iFR) measures.

Blood chemistry tests play a major role in defining cardiac risk factors (ie, serum lipid levels, serum human C-reactive protein level, serum creatinine) and can help with determining the etiology of some symptoms (ie, serum BNP or NT-proBNP level). Myocardial injury is defined based on the presence of released troponin. The use of high-sensitivity troponin has increased awareness of the frequency of some myocardial injury in patients with nonacute coronary syndrome and has been shown to allow for early discharge of patients with chest pain and no evidence for acute coronary syndrome. A number of other biomarkers are also being studied to better quantitate the severity of heart failure, but none have entered routine use as yet (other than BNP and NT-proBNP).

The diagnostic procedures for CAD will be discussed in more depth in the following section on Coronary Heart Disease. Reviewed here is the use of noninvasive testing for noncoronary heart disease.

Echocardiography & Doppler Ultrasound Imaging

Two-dimensional echocardiography provides information regarding all four chamber sizes, regional and global systolic function, and chamber wall thickness (VIDEO 10–2). Excellent images of valve motion, intracardiac masses, abnormal or absent cardiac structures, and pericardial fluid can all be distinguished. Pulsed wave Doppler provides a semiquantitative or qualitative estimation of the severity of transvalvular gradients, RV systolic pressure (based on a tricuspid regurgitation jet velocity), PA pressure, valvular regurgitation severity, and the presence of intracardiac shunts. The Doppler mitral inflow pattern can help confirm diastolic dysfunction and can help verify a restrictive cardiomyopathic picture or constrictive pericarditis. Color flow Doppler provides a visual pattern of blood flow velocities superimposed over the anatomic two-dimensional echocardiographic image. This allows for the demonstration of turbulence from stenotic or regurgitant valves, and for the visualization of intracardiac defects. Since some regurgitant flow occurs normally, especially when the AV valves close, the presence of minor amounts of regurgitant color flow should not be construed as pathology. Tissue Doppler methods help define the extent of either annular or ventricular wall motion independent of intracardiac flow velocity, and the relationship between the two may prove useful for defining diastolic pressure elevation, identifying abnormalities in ventricular contraction or diastolic relaxation, or optimizing pacemaker therapy. The E wave of the mitral inflow Doppler pattern reflects the rate of blood flow from the LA to LV. The E′ of the tissue Doppler reflects how rapid the LV relaxes. The E/E′ ratio increases if the LA pressure pushing blood into the LV is relatively greater than the rate of relaxation. An E/E′ ratio greater than 15–18, therefore, suggests an elevated LA pressure.

Echocardiography with contrast agents that fill both heart chambers improves the visualization of wall motion. Other contrast agents have been developed that produce echocardiographic contrast within the myocardium, providing gross myocardial perfusion data. Such perfusion methods have yet to be standardized and have not found wide acceptance.

The use of Doppler tissue imaging can also provide visual descriptions of wall stress and strain. Measures of longitudinal stress and strain can be displayed visually overlying the image. The value of stress/strain imaging is improving as the techniques have become more standardized; it may be particularly useful in patients where early diastolic dysfunction is present and in defining abnormal myocardium when attempting to separate the athlete’s heart (and associated LV hypertrophy) from a diseased heart (such as hypertrophic cardiomyopathy). Abnormalities have been observed prior to a fall in the LV ejection fraction (LVEF) in patients undergoing chemotherapy. The timing of right and left ventricular contraction can also be measured (cardiac synchronization) and the results have been used to better define the need for biventricular pacing, though recent data suggest its value may be limited.

Transesophageal echocardiography (TEE) with Doppler ultrasound is used to obtain echocardiographic data when surface sound transmission is poor; to derive information about posterior structures (especially the atria or atrial appendage and AV valves), prosthetic heart valves, and intracardiac masses not well seen on chest wall echocardiography (eg, vegetations in endocarditis or thrombi on pacemaker leads). It is standard practice to use TEE to monitor patients during valvular or other structural heart surgery. It can confirm the location of the pulmonary veins and define septal defects or the presence of a patent foramen ovale (PFO). It is superior to surface echocardiography in diagnosing LA appendage thrombi and regurgitant lesions associated with prosthetic valves. It is also quite sensitive in detecting aortic dissection and severe atherosclerosis of the ascending aorta, which may be the source for transient ischemic attacks (TIAs) or embolic strokes (VIDEO 10–3).

Three-dimensional echocardiography allows for visualization of cardiac structures in multiple dimensions, though there remains few diagnoses where transthoracic three-dimensional imaging adds significant value. Three-dimensional echocardiography technology, though, has been a particularly useful adjunct to TEE during invasive cardiac procedures and cardiac surgery, where it helps define the relationships among the various heart structures in real time. In addition, three-dimensional echocardiographic imaging appears to provide improved volumetric data compared to two-dimensional echocardiographic imaging.

Stress echocardiography can be used in valvular as well as ischemic heart disease. Echocardiograms may be performed during or immediately following exercise. Valvular gradient changes after exercise or during dobutamine infusion can be evaluated. Transient segmental wall motion abnormalities during or immediately following exercise or pharmacologic stress suggest ischemia (VIDEO 10–4). Improvement in wall motion during low-dose dobutamine infusions is an indicator of myocardial viability. Changes in the estimated pulmonary pressure and valvular gradients can occasionally help decide whether symptoms are related to valvular disease.

Cardiac MRI & Multislice CT

Cardiac MRI continues to evolve rapidly and its use is expanding. Currently available systems provide high-quality and high-resolution images of cardiac and adjacent vascular structures. Cardiac MRI also provides excellent images that can quantify cardiac function and structure. It is particularly useful for defining myocardial scarring, including the presence of infiltrative myocardial diseases such as sarcoidosis or amyloidosis. Flow measurements, valve orifice sizes, and shunt sizes can all be determined. With the use of gadolinium contrast agents, cardiac MRI can be used to assess myocardial perfusion during adenosine pharmacologic stress and to assess myocardial viability. Contrast-enhanced images can provide accurate measurement of MI size and location. Delayed enhancement following gadolinium administration helps quantify myocardia scar. Cardiac MRI can also provide accurate three-dimensional reconstruction of the great vessels and abdominal aorta. The study can also be used to screen for renal artery stenosis in patients with hypertension. However, patients with pacemakers or defibrillators are not generally believed to be candidates for cardiac MRI, although some groups are willing to perform cardiac MRI in this situation, and there are newer pacemakers that are “MRI compatible.” Intracardiac pacemakers or defibrillators may result in artifacts obscuring the myocardium, though. Nephrogenic systemic fibrosis, a syndrome that leads to skin and organ fibrosis believed to be due to the gadolinium contrast agent, may develop in patients with severe kidney dysfunction. Therefore, acute or chronic kidney disease is considered a relative contraindication to cardiac MRI with gadolinium, although newer contrast agents using tiny superparamagnetic iron particles do not appear to cause nephrogenic systemic fibrosis and can usually provide diagnostic images when hyperenhancement is not needed.

Cardiac multislice CT, at lower resolution, has primarily been used to screen patients for CAD. The extent of calcium within the coronary vessels has been found to correlate with the extent of atherosclerotic CAD. Higher resolution imaging modes and faster acquisition times enable noninvasive coronary angiography to be obtained. The negative predictive value of a negative coronary study is high (around 95%), suggesting that it is an excellent test to confirm normal coronaries. Calcium in the arterial wall may limit its ability to define the severity of coronary disease, but the inherent resolution of cardiac multislice CT allows it to better visualize coronaries than cardiac MRI. Multislice CT, with its impressive three-dimensional reconstruction algorithms, also provides outstanding images in valvular, myocardial, and congenital heart disease. However, there remains some concern regarding the radiation dose with multislice CT, which is not an issue with MRI where there is no ionizing radiation involved. Issues regarding the radiation dosage have been addressed by gating scans with the ECG and acquiring data only in early diastole, for instance. This has led to a reduced concern regarding the dose of radiation and, in general, the radiation dose for CT is similar to that for a diagnostic heart catheterization. In patients in the emergency department with symptoms suggestive of acute coronary syndromes, incorporating imaging of the coronary tree (to exclude CAD), pulmonary arteries (to exclude pulmonary emboli), and the aorta (to exclude aortic dissection) is increasingly performed. The cost-effectiveness of this triple rule out method is being debated. With the publication of the importance of fractional flow reserve in assessing coronary lesions invasively (the FAME trials), the potential ability to obtain fractional flow reserve data noninvasively using coronary CT angiography has led to the growing promise that the coronary CT angiography will provide information regarding the functional significance of individual lesions. This would be a major step forward in the noninvasive assessment of CAD.

Cardiac catheterization continues to evolve from a diagnostic procedure to a therapeutic one, as more and more types of cardiac lesions are now approachable with percutaneous techniques.

Right heart catheterization is convenient to perform in the laboratory, at the bedside, or in the operating room. It allows measurement of RA, RV, PA, and pulmonary capillary wedge pressures (PCWP; the latter an indicator of LA pressure), oxygen saturation, and cardiac output (eFigure 10–13). These data may be used to diagnose intracardiac shunts, the physiological significance of pericardial disease, and right-sided valve lesions. It can help distinguish between cardiac and pulmonary disease. It is useful in pulmonary hypertension to document whether the elevated pressures are related to pulmonary disease or to left heart disease. In those with pulmonary hypertension found due to inherent pulmonary vascular disease, vasodilators can be administered to test for vasoreactivity and provides information as to which pulmonary vasodilators may be effective. Hemodynamic monitoring with a PA catheter may be very helpful in the assessment and treatment of shock, heart failure, complicated MI, respiratory failure, and postoperative hemodynamic instability. However, this procedure is not without risk—complications include pneumothorax, bleeding, arrhythmias, PA rupture, pulmonary emboli, infection, and patient immobility. There is little evidence that use of PA catheters for routine monitoring in heart failure improves clinical outcomes, and therefore is it not commonly used even for patients with shock. It is still useful, though, to monitor acutely ill patients during surgery and in critical care settings, especially when volume status is uncertain. Bedside echocardiography is a more common method to assess ventricular systolic function and to assess for cardiac contribution to a shock state.

Left heart catheterization with standard coronary angiography is performed to assess the cardiac valves and LV function plus the presence and severity of CAD. The approach is equally effective from the radial artery or the femoral artery. Valvular stenosis and regurgitation can be semi-quantitated by hemodynamic and angiographic measurements. The EF and regional wall motion can be assessed by contrast left ventriculography, though this is done much less often currently, as noninvasive measures, such as echocardiography, have supplanted the need for this to be done. Direct hemodynamics measurements are often helpful when the clinical scenario and echocardiography/Doppler data are either not definitive or there is a discrepancy between the echocardiography/Doppler information and either the examination or symptoms.

Both coronary and noncoronary interventions are now common in the cardiac catheterization laboratory. Acute interventions include simple coronary balloon angioplasty (rarely done currently), and coronary stenting (nearly universally used), typically with stents coated with agents to inhibit endothelial growth—termed drug-eluting stents— in an effort to reduce endothelial proliferation and stenosis within the stent. Coronary interventions are performed routinely in the acute as well as chronic setting. Other novel interventional procedures include balloon valvuloplasty (primarily for pulmonic or mitral valve stenosis); stenting or ballooning (or both) of coarctation or branch PA stenosis; percutaneous occlusion of intracardiac defects, such as ASD, PFO or patent ductus arteriosus; or alcohol ablation of the subaortic septum in hypertrophic cardiomyopathy. While clinical trials continue on percutaneous replacement of the pulmonary and aortic valves, the US Food and Drug Administration (FDA) has approved the Melody and the SAPIEN valve for certain pulmonary valve replacements (over 10,000 have been implanted worldwide) and both the Edwards SAPIEN stented valve and the Medtronic CoreValve for percutaneous aortic valve replacement (AVR) in both high risk (greater than 8% mortality) and intermediate risk (4–8% mortality) patients, and now in low-risk patients (less than 4% mortality) with severe aortic stenosis. Both devices have also been approved for valve-in-valve procedures wherein they are being used to treat patients with a prior bioprosthetic valve stenosis in either the mitral or aortic position. An estimated 500,000 percutaneous aortic valve procedures (called transcatheter aortic valve replacement [TAVR] and sometimes called transcatheter aortic valve intervention [TAVI]) have been performed worldwide. Its use in those with bicuspid aortic valve stenosis is still not resolved, though many patients with bicuspid aortic valve stenosis have done well after undergoing TAVR. Its use in aortic regurgitation is still somewhat unclear, however, with mixed results reported.

The same technology as described above (ie, using coronary CT images) for the assessment of coronary lesion stenosis severity is being investigated in the cardiac catheterization laboratory. Using only the angiographic information, it may be possible to measure the pressure drop across the coronary lesion (the FFR or iFR) without the use of a pressure wire. This would reduce the risk of the use of the pressure wire and allow for functional assessment of the coronary lesion using angiography alone.