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CHAPTER 4 Diagnostic Tests and Procedures in the Patient With Cardiovascular Disease

Fig. 4.10 Doppler tracing in a patient with aortic stenosis and regurgi-

tation. The velocity of systolic ﬂow is related to the severity of obstruction.

Fig. 4.11 Color Doppler recording demonstrates severe mitral regurgi-

tation. The regurgitant jet seen in the left atrium is represented in blue because blood ﬂow is directed away from the transducer. The yellow components are the mosaic pattern traditionally assigned to turbulent or high-velocity ﬂow. The arrow points to the hemisphere of blood accelerating proximal to the regurgitant oriﬁce (i.e., proximal isovelocity surface area [PISA]). The size of the PISA can be used to help grade the severity of regurgitation. Video 4.2 shows a dynamic echocardiographic image in a patient with mitral regurgitation. LA, Left atrium; LV, left ventricle. (Image courtesy Sheldon E. Litwin, MD, Division of Cardiology, University of Utah, Salt Lake City, Utah.)

NUCLEAR CARDIOLOGY

The traditional radiotracer approach to assess ventricular function is equilibrium radionuclide angiocardiography (ERNA), which uses technetium-99m-labeled red blood cells. Serial ERNA can be performed at rest and during various levels of exercise of pharmacologic perturbations to evaluate ventricular function and reserve. ERNA has high reproducibility because there are no geometric assumptions and there is much less operator dependence in the image acquisition. Diastolic parameters can be readily assessed from the ventricular volume curve, which may be very helpful in the assessment of diastolic dysfunction.

In radionuclide imaging of the heart, patients are injected with a radioactive tracer, which distributes throughout the myocardium in proportion to blood ﬂow. Highly specialized cameras then capture the

distribution of the radioactive tracer, which allows for quantiﬁcation of left ventricular size, systolic function, and myocardial perfusion, depending on the tracer used. The two main types of myocardial imaging used in cardiology, often in stress testing, are single-photon emission tomography (SPECT) and positron emission tomography (PET).

In SPECT imaging, images of the heart are obtained for qualitative and quantitative analyses at rest and after stress (i.e., exercise or pharmacologic vasodilation). Radionuclide tracers are injected prior to rest images and just prior to the completion of stress. The most frequently used radionuclide in SPECT imaging is technetium-99m sestamibi. In the normal heart, the radioisotope is equally distributed throughout the myocardium at rest and stress. In patients with ischemia, a localized area of decreased radiotracer uptake occurs after stress but may partially or completely reverse during rest. A persistent defect at peak exercise and rest (i.e., ﬁxed defect) is consistent with MI or scarring.

The use of new approaches such as combined low-level exercise and vasodilators, prone imaging, attenuation correction, and computerized data analysis has improved the quality and reproducibility of the data from these studies. New camera technologies, including those with solid state detector arrays, have demonstrated improved image resolution and allow for reduced radiation exposure. Myocardial perfusion imaging may also be combined with ECG-gated image acquisition (gated SPECT) to allow simultaneous assessment of ventricular function and perfusion. Using this technique, regional wall motion can be evaluated to help assess potential perfusion defects (Video 4.5).

PET has been widely used in oncology for many years but has become increasingly popular in cardiology (Video 4.5). The commonly used tracers in cardiac PET imaging include rubidium-82 and ﬂuorine-18 ﬂuorodeoxyglucose (FDG). When compared to SPECT, PET has several technical advantages, including higher spatial and temporal resolution, less radiation exposure, and the ability to quantify absolute rather than relative coronary blood ﬂow. These advantages mean that PET is more sensitive and speciﬁc compared to SPECT in diagnosing coronary disease, especially in the presence of multivessel disease. Additionally, because PET gives an absolute rather than relative quantiﬁcation of coronary blood ﬂow, it can be used to assess abnormal microvascular coronary circulation. Despite these clinical advantages of PET over SPECT, the lack of availability of PET cameras and radiotracers, as well as high costs and reimbursement issues, limits the widespread adoption of PET.

In patients with suspected cardiac sarcoidosis, FDG-PET is the imaging modality of choice for diagnosis. FDG-PET can also be used to detect myocardial viability by the use of perfusion and metabolic tracers. In patients with left ventricular dysfunction, metabolic activity in a region of myocardium supplied by a severely stenotic coronary artery suggests viable tissue that may regain more normal function after revascularization (Fig. 4.14).

CARDIAC MAGNETIC RESONANCE IMAGING

Cardiac magnetic resonance imaging (cMRI) is a noninvasive method that is increasingly used for studying the heart and vasculature and has, in fact, become the gold standard for measuring myocardial function, volumes, and scarring. cMRI offers high-resolution dynamic and static images of the heart that can be obtained in any plane, allowing quantiﬁcation of left ventricular and valvular function. High-quality images can be obtained in a larger proportion of subjects than is typically possible with echocardiography. Obesity, claustrophobia, inability to perform multiple breath-holds of 10 to 20 seconds, and arrhythmias are causes of reduced image quality.

34 SECTION II Cardiovascular Disease

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Fig. 4.12 Echocardiogram enhanced with intravenous ultrasound contrast agent: apical four-chamber view

(A) and apical long-axis view (B). Highly echo-reﬂectant microbubbles make the left ventricular cavity appear white, whereas the myocardium appears dark. Video 4.3 shows a dynamic image of echocardiographic contrast. (Image courtesy Sheldon E. Litwin, MD, Division of Cardiology, University of Utah, Salt Lake City, Utah.)

Fig. 4.13 Transesophageal echocardiogram demonstrates a vegetation (arrow) adherent to the ring of a

bileaﬂet, tilting-disk mitral valve prostheses. (A) In systole, the leaﬂets are closed with the vegetation seen in the left atrium. (B) In diastole, the leaﬂets are open, with the vegetation prolapsing into the left ventricle. Transesophageal echocardiography is the diagnostic test of choice for assessing prosthetic mitral valves because the esophageal window allows unimpeded views of the atrial surface of the valve. Video 4.4 shows a dynamic transesophageal echocardiographic image. LA, Left atrium; LV, left ventricle; MV, prosthetic mitral valve disks; V, vegetation. (Courtesy Sheldon E. Litwin, MD, Division of Cardiology, University of Utah, Salt Lake City, Utah.)

cMRI also offers signiﬁcant advantages over other imaging techniques for the characterization of tissues (e.g., muscle, fat, scar). cMRI is useful in the evaluation of ischemic heart disease because stress-rest myocardial perfusion (Fig. 4.15A) and areas of prior infarction (see

Fig. 4.15B to D) can be visualized with excellent spatial resolution.

Delayed or late gadolinium enhancement (LGE) in the myocardium

HCM, speciﬁc patterns on MRI can help identify those patients at highest risk of sudden cardiac death who would require deﬁbrillators. Similarly, MRI has also been used to help assess right ventricular morphology and function in patients with suspected arrhythmogenic right ventricular cardiomyopathy. The role of MRI in all aspects of cardiac

imaging continues to grow. is characteristic of scar or permanently damaged tissue (Video 4.6). The greater the transmural extent of LGE is in a given segment, the lower the likelihood of improved function in that segment after revascularization. Because of the better spatial resolution, LGE can identify localized or subendocardial scars that are not detectable with nuclear imaging techniques.

MRI is excellent for evaluating a variety of cardiomyopathies (Fig.

4.16). In addition to morphology and function, characteristic patterns

of LGE have been reported in myocarditis, cardiac amyloidosis, sarcoidosis, and hypertrophic cardiomyopathy (HCM). In patients with

STRESS TESTING

Stress testing is an important noninvasive tool for evaluating patients

with known or suggested coronary artery disease (CAD). During exer-

cise, the increased demand for oxygen by the working skeletal mus-

cles is met by increases in heart rate and cardiac output. In patients

with signiﬁcant CAD, the increase in myocardial oxygen demand

cannot be met by a proportional increase in coronary blood ﬂow, and

myocardial ischemia may produce chest pain and characteristic ECG

CHAPTER 4 Diagnostic Tests and Procedures in the Patient With Cardiovascular Disease

[13N]-ammonia

F]-deoxyglucose

[

N]-ammonia

F]-deoxyglucose

[

N]-ammonia

[

F]-deoxyglucose

Fig. 4.14 Resting myocardial perfusion (obtained with [13N]-ammonia) and metabolism (obtained with

[18F]-deoxyglucose) is seen in positron emission tomography images of a patient with ischemic cardiomyopathy. The study demonstrates a perfusion-metabolic mismatch (reﬂecting hibernating myocardium) in which large areas of hypoperfused (solid arrows) but metabolically viable (open arrows) myocardium involve the anterior, septal, and inferior walls and the left ventricular apex. Video 4.5 shows a dynamic image obtained with cardiac single-photon emission computed tomography imaging. (Courtesy Marcelo F. Di Carli, MD, Brigham and Women’s Hospital, Boston, Mass.)

abnormalities. Combined with the hemodynamic response to exercise, these changes can give useful diagnostic and prognostic information for the patient with cardiac abnormalities. The most common indications for stress testing include establishing a diagnosis of CAD in patients with chest pain, assessing prognosis and functional capacity of patients with chronic stable angina or after an MI, evaluating exercise-induced arrhythmias, and assessing for ischemia after a revascularization procedure. Contraindications to stress testing include acute coronary syndromes, poorly controlled hypertension (blood pressure >220/110 mm Hg), severe aortic stenosis (valve area <1.0 cm2), and decompensated congestive heart failure.

When to Stress Symptomatic Patients

Stress testing is most often used to evaluate symptoms concerning for ﬂow-limiting coronary artery disease and make the diagnosis of CAD. The diagnostic accuracy of the stress test depends on several factors, including the pretest probability of CAD in a given patient, the sensitivity and speciﬁcity of the test results in that patient population, the adequacy of stress, and the criteria used to deﬁne a positive test. Stress

testing, when used to diagnose CAD, is one of the most useful and cost-effective tests in symptomatic patients who have an intermediate pretest probability of CAD, which is deﬁned as a 10% to 90% risk. This is because in patients with a low pretest probability, a positive test does not signiﬁcantly increase the post-test probability of CAD, and in patients with a high pretest probability, a negative test does not signiﬁcantly decrease the post-test probability of CAD. The pretest probability of CAD can be calculated through a variety of scores but is most commonly done based on a patient’s description of angina (Table 4.4).

Angina has three important components:

1. Substernal chest pain or discomfort

2. The pain or discomfort is provoked by exertion or emotional stress

3. The pain or discomfort is relieved by rest and/or nitroglycerin. Patients with all three components are said to have typical angina. Those with any two of the three components have atypical angina, and patients with nonanginal chest pain have only one or none of these components.

Other factors that are not solely based on the description of chest

discomfort may be present that would increase a patient’s pretest

36 SECTION II Cardiovascular Disease

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Fig. 4.15 Use of cardiac magnetic resonance imaging in the evaluation of chest pain or ischemic heart dis-

ease. (A) First-pass perfusion study during vasodilator stress shows a large septal perfusion defect (arrow). The hypoperfused area appears dark compared with the myocardium with normal perfusion. (B) Example of delayed enhancement imaging of an almost transmural infarction of the mid-inferolateral wall, including the posterior papillary muscle. Infarcted myocardium appears white, whereas normal myocardium is black (arrow). (C) Nontransmural (subendocardial) infarction of the septum and apex (arrow). (D) Patient with acute myocarditis mimicking an acute coronary syndrome. Midmyocardial, rather than subendocardial, delayed enhancement is characteristic of myocarditis (arrow).

probability of CAD. These include baseline ECG abnormalities suggestive of CAD and multiple CAD risk factors, such as diabetes, smoking, hypertension, dyslipidemia, or family history of premature CAD. These should be taken into consideration on an individual basis and may require an upward revision of pretest probability.

Stress Modalities

There are two essential components to any stress test: the type of stress and the imaging modality. Stress can either be exercise-induced or pharmacologic. Exercise level is deemed adequate if the patient achieves 85% of his or her maximal predicted heart rate. Submaximal stress tests can still be interpreted but may be limited in the ability to rule out disease due to decreased sensitivity. Indications for terminating a stress test include fatigue, severe hypertension (>220 mm Hg systolic), worsening angina during exercise, developing marked or widespread ischemic ECG changes, signiﬁcant arrhythmias, or hypotension.

For patients who are able to exercise, the most commonly used exercise protocols are the Bruce and modiﬁed Bruce protocols. These protocols require a patient to walk on a treadmill as the speed and incline of the belt increases with each advancing stage. Any patient who can exercise should do so, as duration of exercise and provoked symptoms provide valuable clinical and prognostic information for the physician. The modiﬁed Bruce or similar protocols are ideal for older, overweight, unstable, or debilitated patients. Additionally, in patients

unable to exercise on a treadmill, bicycle or arm ergometer testing may also be used. In patients who cannot exercise or in those where exercise will interfere with image acquisition, pharmacologic agents may be used.

The most commonly used pharmacologic stress agents are dobutamine, adenosine, and regadenoson, an adenosine derivative and selective adenosine A2A receptor agonist. Dobutamine is a synthetic sympathomimetic that stimulates alpha-1, beta-1, and beta-2 receptors, increasing inotropy and chronotropy, thereby increasing myocardial oxygen demand. It should be used cautiously in patients with a history of atrial or ventricular arrhythmias as it can exacerbate both. Regadenoson is an adenosine receptor agonist that induces coronary vasodilation and is more commonly used in radionuclide myocardial perfusion imaging. Its use is contraindicated in patients with asthma or COPD and active wheezing as well as patients with signiﬁcant bradyarrhythmias without a pacemaker. It should be used with caution in patients with a history of seizures as it can lower the seizure threshold.

STRESS IMAGING

Exercise or pharmacologic stress testing must be combined with imaging modalities to assess for characteristic changes seen in ﬂow-limiting coronary artery disease. The most basic form of imaging is an ECG, which can be combined with adjunctive echocardiography or radionuclide imaging to increase the diagnostic accuracy of the testing.

CHAPTER 4 Diagnostic Tests and Procedures in the Patient With Cardiovascular Disease

Fig. 4.16 Cardiac magnetic resonance imaging (MRI) is used in the evaluation of cardiomyopathies. (A)

Severe left ventricular hypertrophy in a patient with hypertrophic cardiomyopathy. Diastolic frame shows open mitral valve (arrow). (B) Systolic frame shows systolic anterior motion of the mitral valve with ﬂow disturbance in the left ventricular outﬂow tract (arrow). (C) Patient has left ventricular noncompaction as evidenced by deep trabeculations in the left ventricular apex (arrow). (D) Patient with ischemic cardiomyopathy has transmural apical infarction and adjacent mural thrombus (arrow). Video 4.6 shows a dynamic cardiac MRI image. (Images courtesy Sheldon E. Litwin, MD, Division of Cardiology, University of Utah, Salt Lake City, Utah.)

TABLE 4.4 Diamond and Forrester Pretest Probability of Coronary Artery Disease by Age, Sex,

and Symptoms

Age (Years) Sex Typical/Definite Angina Pectoris Atypical/Probable Angina Pectoris Nonanginal Chest Pain

≤39 Men Intermediate Intermediate Low

Women Intermediate Very low Very low

40-49 Men High Intermediate Intermediate

Women Intermediate Low Very low

50-59 Men High Intermediate Intermediate

Women Intermediate Intermediate Low

≥60 Men High Intermediate Intermediate

Women High Intermediate Intermediate

High: >90% pretest probability. Intermediate: between 10% and 90% pretest probability. Low: between 5% and 10% pretest probability. Very low: <5% pretest probability. From Wolk MJ, Bailey SR, Doherty JU, et al: ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 Multimodality Appropriate Use Criteria for the Detection and Risk Assessment of Stable Ischemic Heart Disease. Journal of the American College of Cardiology 63:380-406, 2014.

38 SECTION II Cardiovascular Disease

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Stress Electrocardiography

The normal physiologic response to exercise is an increase in heart rate and systolic and diastolic blood pressures. The ECG maintains normal T-wave polarity, and the ST segment remains unchanged or, if depressed, has a rapid upstroke back to baseline. An ischemic ECG response to exercise is deﬁned as 1.5 mm of upsloping ST-segment depression measured 0.08 second past the J point, at least 1 mm of horizontal ST depression, or 1 mm of downsloping ST-segment depression measured at the J point. Given the large amount of artifact on the ECG that may occur with exercise, these changes must be seen in at least three consecutive depolarizations. Other ﬁndings that suggest more extensive CAD include early onset of ST depression (6 minutes); marked, downsloping ST depression (>2 mm), especially if present in more than ﬁve leads; ST changes persisting into recovery for more than 5 minutes; and failure to increase systolic blood pressure to 120 mm Hg or more or a sustained decrease of 10 mm Hg or more below baseline.

The ECG is not diagnostically useful in the setting of left ventricular hypertrophy, LBBB, Wolff-Parkinson-White syndrome, or chronic digoxin therapy. In these instances, further imaging modalities such as echocardiography, nuclear imaging, or positron-emission tomography (PET) are needed to help diagnose ischemia.

Stress Echocardiography

Two-dimensional echocardiography and Doppler echocardiography are often used in conjunction with exercise or pharmacologic stress testing. The pharmacologic agent typically used is dobutamine. A baseline echocardiogram is performed at rest and during stress. Changes in wall motion are indicative of ischemia and coronary artery disease. In areas of the left ventricle that have wall motion abnormalities at rest, improvement of these wall motion abnormalities with exercise or lowdose dobutamine is indicative of viability.

Relative to myocardial perfusion imaging, the sensitivity of stress echocardiography is slightly lower whereas the speciﬁcity is slightly higher. A poor baseline echocardiogram due to limited acoustic windows will limit stress test results. The estimated cost-effectiveness of stress echocardiography is signiﬁcantly better than nuclear perfusion imaging because of the overall lower cost.

Myocardial Perfusion Imaging (See Also Nuclear Cardiology Section)

Stress testing, using myocardial perfusion imaging with SPECT to compare relative coronary blood ﬂow at stress and at rest, helps to identify areas of perfusion mismatch, indicative of ischemia. Like with other stress modalities, exercise or pharmacologic stress can be used. Commonly used pharmacologic agents include dipyridamole, adenosine, and regadenoson, which are all coronary vasodilators. It is important to note that patients with LBBB have to undergo pharmacologic stress when receiving myocardial perfusion imaging, even if they are able to exercise, as the abnormal septal motion caused by the LBBB can lead to a false perfusion defect during exercise.

Stress Cardiac Magnetic Resonance Imaging

Though either exercise or pharmacologic stress may be combined with cMRI, the contemporary use of stress cMRI usually refers to stress perfusion cMRI with gadolinium contrast that is performed with regadenoson. This technique allows for evaluation of wall motion, perfusion, scar, viability, and microvascular dysfunction, as well as chamber quantiﬁcation and function, allowing for a comprehensive evaluation of the myocardium and myocardial function. Changes in late gadolinium enhancement between rest and stress has performance characteristics for diagnosing CAD that are at least as good and likely superior to

those of conventional stress tests using nuclear myocardial perfusion imaging or echocardiography, and on par with PET imaging.

COMPUTED TOMOGRAPHY OF THE HEART

Newer applications of computed tomography (CT) have greatly advanced our ability to diagnose cardiovascular disease noninvasively. The development of fast gantry rotation speeds and the addition of multiple rows of detectors (i.e., multidetector CT) have allowed unprecedented visualization of the great vessels, heart, and coronary arteries with images acquired during a single breath-hold lasting 10 to 15 seconds. CT is used to diagnose aortic aneurysm, acute aortic dissection, and pulmonary embolism, and it is useful for deﬁning congenital abnormalities and detecting pericardial thickening or calciﬁcation associated with constrictive pericarditis. ECG-gated dynamic CT images have been used to quantify ventricular size, function, and regional wall motion (Video 4.7), and in contrast to echocardiography, CT is not limited by lung disease or chest wall deformity. However, obesity and implanted prosthetic materials (i.e., mechanical valves or pacing wires) may affect image quality.

The greatest excitement and controversy about cardiac CT relates to the evaluation of coronary atherosclerosis. Electron beam and multidetector CT scans can be used to quickly and reliably visualize and quantitate the extent of coronary artery calciﬁcation (Fig. 4.17). The presence of coronary calcium is pathognomonic of atherosclerosis, and the extent of coronary calcium (usually reported as an Agatston score) is a powerful marker of future cardiovascular events. The coronary calcium score adds substantial, independent improvement in risk prediction to the commonly employed clinical risk scores (e.g., Framingham risk score). Moreover, the calcium score is a good marker of the overall atherosclerotic burden. Indications for coronary calcium scoring continue to grow, especially in reﬁning risk predictions in asymptomatic patients at intermediate risk for arteriosclerotic cardiovascular disease.

Contrast-enhanced coronary computed tomography angiography (CCTA) has improved dramatically in recent years. CCTA has a sensitivity of more than 95% in diagnosing signiﬁcant coronary artery obstruction. Unlike myocardial perfusion imaging, CCTA is an anatomic test, and thus does not give information on perfusion or blood ﬂow across a lesion. Thus, in patients with known coronary disease, CCTA cannot easily differentiate between ischemic and nonischemic chest pain. New technology is being developed to noninvasively determine the hemodynamic signiﬁcance of a lesion through CCTA, similar to fractional ﬂow reserve in coronary catheterization, though this technology still needs to be rigorously tested and standardized. Evaluation of coronary arteries with CCTA can be signiﬁcantly limited in patients with extensive coronary calciﬁcations, cardiac devices, or prior stents due to technical limitations.

Concerns that limit the widespread use of cardiac CT most frequently cite the risks of radiation and contrast exposure and the lack of prospective studies showing improvement in outcome with this testing modality. In early studies, the calculated radiation exposure of CCTA was about double that of a diagnostic invasive coronary angiogram, although with prospective ECG-gating, most studies are now equal to or less than a diagnostic angiogram. Contrast use is often higher in a CCTA than in a diagnostic invasive coronary angiogram. The role of CCTA in routine clinical practice continues to evolve.

CARDIAC CATHETERIZATION

Cardiac catheterization is an invasive technique in which ﬂuid-ﬁlled catheters are introduced percutaneously into the arterial and/or venous circulation. This method allows direct measurement of intracardiac

CHAPTER 4 Diagnostic Tests and Procedures in the Patient With Cardiovascular Disease

Fig. 4.17 Computed tomography coronary angiography compared with conventional radiographic contrast

angiography. (A and B) Volume-rendering technique demonstrates stenosis of the right coronary artery and normal left coronary artery. (C and D) Maximal intensity projection of the same arteries demonstrates severe noncalciﬁed plaque in the right coronary artery with superﬁcial calciﬁed plaque. (E and F) Invasive angiography of the same arteries. (From Raff GL, Gallagher MJ, O’Neill WW, et al: Diagnostic accuracy of noninvasive coronary angiography using 64-slice spiral computed tomography, J Am Coll Cardiol 46:552-557, 2005.)

pressures and oxygen saturation and, with the injection of a contrast agent, visualization of the coronary arteries, cardiac chambers, and great vessels. Cardiac catheterization is indicated when a clinically suggested cardiac abnormality requires conﬁrmation and its anatomic and physiologic importance needs to be quantiﬁed. Coronary angiography for the diagnosis of CAD is the most common indication for this test.

Compared with catheterization, noninvasive testing with echocardiography is safer, often cheaper, and equally effective in the evaluation of most valvular and hemodynamic conditions. Most often, catheterization precedes some type of beneﬁcial intervention, such as

coronary artery angioplasty, coronary bypass surgery, or valvular surgery. Although cardiac catheterization is usually safe (0.1% to 0.2% overall mortality rate), procedure-related complications such as vascular injury, renal failure, stroke, and MI can occur.

Left Heart Catheterization and Coronary Angiography

Left heart catheterization and coronary angiography ﬁrst requires the introduction of wires and ﬂuid-ﬁlled catheters into the arterial system of the body. In the past, femoral arterial access was the default route, but now, radial arterial access has become increasingly more common.

Cardia

Oxygen consumption

oxygen content)

mm Hg

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40 SECTION II Cardiovascular Disease

200

100

Fig. 4.18 Electrocardiographic tracing and left ventricular (LV) and aortic

(AO) pressure curves in a patient with aortic stenosis. A pressure gradient occurs across the aortic valve during systole.

It has replaced femoral arterial access as the default access site in most centers. Radial arterial access is associated with less bleeding, fewer vascular complications, and increased patient comfort and early mobility after the procedure when compared with femoral arterial access. However, it is also associated with higher radiation exposure and increased procedural time.

After access is obtained, wires and ﬂuid-ﬁlled catheters are advanced to the aortic root and through the aortic valve into the left ventricle under ﬂuoroscopic guidance. Here, left ventricular size, wall motion, and ejection fraction can be accurately assessed by injecting contrast into the left ventricle (i.e., left ventriculography). Aortic and mitral valve insufﬁciency can be qualitatively assessed during angiography by observing the reﬂux of contrast medium into the left ventricle and left atrium, respectively. Left ventricular pressures can be directly measured and recorded, and the catheter can slowly be pulled back across the left ventricular outﬂow tract (LVOT) and aortic valve to directly assess for any pressure differential that would be consistent with aortic stenosis or LVOT obstruction (Fig. 4.18).

The coronary anatomy can be deﬁned by injecting contrast medium into the coronary tree. Atherosclerotic lesions appear as narrowing of the internal diameter (lumen) of the vessel. A hemodynamically important stenosis is deﬁned as 70% or more narrowing of the luminal diameter. However, the hemodynamic signiﬁcance of a lesion can be underestimated by coronary angiography, particularly when the atherosclerotic plaque is eccentric or elongated. Intravascular ultrasound, optical coherence tomography, or miniaturized pressure sensors can be used during invasive procedures to help evaluate the severity or estimate the physiologic signiﬁcance of intermediate lesions.

Right Heart Catheterization

Right heart catheterization is a useful invasive technique that can be performed at bedside or with ﬂuoroscopic guidance. The pulmonary artery (Swan-Ganz) catheter, which is a balloon-tipped catheter used for right heart catheterization, can be left in a patient for a prolonged period of time in a critical care setting to provide continuous information on cardiovascular hemodynamics and ﬁlling pressures. Right heart catheterization can be helpful when used in appropriate situations, such as when differentiating noncardiogenic from cardiogenic

pulmonary edema, managing mixed shock, managing cardiogenic shock, and classifying and treating pulmonary hypertension.

Right heart catheterization is performed by ﬁrst accessing the venous system. Common sites of entry for right heart catheterization include the internal jugular vein (usually the right), the right brachial vein, or the femoral veins. The procedure can be performed at the bedside or under ﬂuoroscopic guidance with a balloon-tipped (Swan-Ganz) catheter. The catheter is advanced from the vein to the right atrium, right ventricle, and pulmonary artery, where pressures are measured and recorded. The catheter can then be advanced further until it wedges in the distal pulmonary artery. The transmitted pressure measured in this location originates from the pulmonary venous system and is known as the pulmonary capillary wedge pressure. In the absence of pulmonary venous disease, the pulmonary capillary wedge pressure reﬂects left atrial pressure, and if no signiﬁcant mitral valve pathologic condition exists, it reﬂects left ventricular diastolic pressure. A more direct method of obtaining left ventricular ﬁlling pressures is through left heart catheterization, as described in the previous section. With these two methods of obtaining intracardiac pressures, each chamber of the heart can be directly assessed and the gradients across any of the valves determined (Fig. 4.19).

Cardiac output can be determined by one of two widely accepted methods: the Fick oxygen method and the indicator dilution technique. The basis of the Fick method is that total uptake or release of a substance by an organ is equal to the product of blood ﬂow to that organ and the concentration difference of that substance between the arterial and venous circulation of that organ. If this method is applied to the lungs, the substance released into the blood is oxygen; if no intrapulmonary shunts exist, pulmonary blood ﬂow is equal to systemic blood ﬂow or cardiac output. The cardiac output can be determined by the following equation:

c output =

(Arterial oxygen content _ Venous

Oxygen consumption is measured in milliliters per minute by collecting the patient’s expired air over a known period while simultaneously measuring oxygen saturation in a sample of arterial and mixed venous blood (i.e., arterial and venous oxygen content, respectively, measured in milliliters per liter). The cardiac output is expressed in liters per minute and then corrected for body surface area (i.e., cardiac index). The normal range of cardiac index is 2.6 to 4.2 L/min/m2. Cardiac output can also be determined by the indicator dilution technique, which most commonly uses cold saline as the indicator. With this method, cold saline is injected into the blood, and the resulting temperature change downstream is monitored. This action generates a curve in which temperature change is plotted over time, and the area under the curve represents cardiac output.

Detection and localization of intracardiac shunts can be performed by sequential measurement of oxygen saturation in the venous system, right side of the heart, and two main pulmonary arteries. In patients with left-to-right shunt ﬂow, an increase in oxygen step-up (i.e., saturation increase from one chamber to the successive chamber) occurs as arterial blood mixes with venous blood. By using the Fick method for calculating blood ﬂow in the pulmonary and systemic systems, the shunt ratio can be calculated. Noninvasive approaches have largely supplanted catheterization laboratory assessment of shunts.

In the past, the Swan-Ganz catheter was routinely used in most patients with shock; however, randomized trials have since been published suggesting no improvement in outcomes in critically ill patients in whom pulmonary artery catheterization was performed.

CHAPTER 4 Diagnostic Tests and Procedures in the Patient With Cardiovascular Disease

ECG

Radial artery

pressure (mm Hg)

100

Pulmonary

capillary

pressure (mm Hg)

wedge

Right atrial

pressure (mm Hg)

Fig. 4.19 Electrocardiographic (ECG) (A) and Swan-Ganz ﬂotation catheter (C) recordings are shown. The

recordings of a catheter in the radial artery and Swan-Ganz ﬂoating catheter in the right atrium are shown in B and D, respectively. The left portion of tracing C was obtained with the balloon inﬂated, yielding the pulmonary arterial wedge pressure. The right portion of tracing C was recorded with the balloon deﬂated, depicting the pulmonary arterial pressure. In this patient, the pulmonary arterial wedge pressure (i.e., left ventricular ﬁlling pressure) is normal, and the pulmonary artery pressure is elevated because of lung disease.

Certainly, improvements in noninvasive imaging techniques have made the Swan-Ganz catheter much less important in diagnosing cardiac conditions such as cardiac tamponade, constrictive pericarditis, right ventricular infarction, and ventricular septal defect. This led to a decline in the routine use of Swan-Ganz catheters in intensive care units. However, the use of these catheters has resurged, likely due to the increased use of advanced heart failure therapies and mechanical support, where continuous hemodynamic monitoring is essential for optimal therapy titration (Table 4.5).

ENDOMYOCARDIAL BIOPSY

Biopsy of the right ventricular endomyocardium can be performed. With this technique, a bioptome is introduced into the venous system through the right internal jugular vein and guided into the right

ventricle by ﬂuoroscopy. Small samples of the endocardium are taken for histologic evaluation. The primary indication for endomyocardial biopsy is the diagnosis of rejection after cardiac transplantation and documentation of cardiac amyloidosis; however, endomyocardial biopsy may have some use in diagnosing speciﬁc etiologic agents responsible for myocarditis.

NONINVASIVE VASCULAR TESTING

Assessment for the presence and severity of peripheral vascular disease is an important component of the cardiovascular evaluation. Comparison of the systolic blood pressure in the upper and lower extremities is one of the simplest tests to detect hemodynamically important arterial disease. Normally, the systolic pressure in the thigh is similar to that in the brachial artery. An ankle-to-brachial pressure

42 SECTION II Cardiovascular Disease

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TABLE 4.5 Differential Diagnosis Using a Bedside Balloon Flow-Directed (Swan-Ganz) Catheter

Thermodilution Cardiac

Disease State

Cardiogenic shock ↓ ↑ nl or ↓ ↑ Systemic vascular resistance Septic shock (early) ↑ ↓ ↓ ↑ Systemic vascular resistance; myocardial

Volume overload nl or ↑ ↑ ↑ Volume depletion ↓ ↓ ↓ Noncardiac pulmonary edema nl nl nl Pulmonary heart disease nl or ↑ nl ↑ ↑ PA pressure RV infarction ↓ ↓ or nl ↑ Pericardial tamponade ↓ nl or ↑ ↑ Equalization of diastolic RA, RV, PA, and

Papillary muscle rupture ↓ ↑ nl or ↑ Ventricular septal rupture ↑ ↑ nl or ↑ Artifact caused by RA → PA sampling higher

nl, Normal; PA, pulmonary artery; PCW, pulmonary capillary wedge; RA, right atrium; RV, right ventricle; ↑, increased; ↓, decreased.

Output PCW Pressure RA Pressure Comments

dysfunction can occur late

PCW pressure

Large v waves in PCW tracing

in PA than RA; may have large v waves in PCW tracing

ratio (i.e., ankle-brachial index) of less than or equal to 0.9 is abnormal. Patients with claudication usually have an index ranging from 0.5 to 0.8, and patients with rest pain have an index less than 0.5. In some patients, measuring the ankle-brachial index after treadmill exercise may help to determine the importance of borderline lesions. During normal exercise, blood ﬂow increases to the upper and lower extremities with corresponding decreases in peripheral vascular resistance, whereas the overall ankle-brachial index remains unchanged. In the presence of a hemodynamically signiﬁcant lesion, the reduced ﬂow across the lesions causes a consequent pressure decrease, and as a result, the ankle-brachial index decreases in proportion to the severity of the stenosis. Some patients, especially those with diabetes or chronic kidney disease, may have falsely elevated ankle-brachial indices due to vascular stiffness (>1.3). In these patients, a toe-brachial index can be measured. In general, a toe-brachial index less than 0.6 indicates abnormal perfusion in the foot, though the site of the occlusive disease would have to be identiﬁed with further studies.

After signiﬁcant vascular disease in the extremities has been identiﬁed, plethysmography can be used to determine the location and severity of the disease. With this method, a pneumatic cuff is positioned on the leg or thigh, and when inﬂated, temporarily obstructs venous return. Volume changes in the limb segment below the cuff are converted to a pressure waveform, which can be analyzed. The degree of amplitude reduction in the pressure waveform corresponds to the severity of arterial disease at that level.

Doppler ultrasound uses reﬂected sound waves to identify and localize stenotic lesions in the peripheral arteries. This test is particularly useful for patients with severely calciﬁed arteries, for whom pneumatic compression is not possible and ankle-brachial indices are inaccurate. In combination with real-time imaging (i.e., duplex imaging), this technique is useful in assessing speciﬁc arterial segments and bypass grafts for stenotic or occlusive lesions.

Magnetic resonance angiography and CTA allow high-quality and comprehensive imaging of the entire peripheral arterial circulation in

a single study. The three-dimensional nature of these studies and the ability to perform extensive postprocessing views, including cross-sectional views, of all vessels, even those that are very tortuous, are attractive features of these modalities.