Stress Cardiovascular Magnetic Resonance: Wall Motion

Intravenous Dobutamine and Atropine

Developed in 1975 by Tuttle and Mills, dobutamine is a synthetic beta-1-selective catecholamine agonist that binds to myocyte beta-1-receptors and increases intracellular calcium concentrations and myocardial contraction. Dobutamine was first employed as a stress-testing agent in 1984. In addition to enhancing myocardial contractility, it increases the heart rate by promoting peripheral vasodilation and a reflex tachycardia.

Because of rapid metabolism by catechol- O -methyltransferase, dobutamine's onset of action and half-life are both approximately 2 minutes; inactive metabolites are readily excreted by the kidneys and liver. At low doses, <10 µg/kg/min, myocardial contractility is augmented and minor peripheral vasodilation occurs. As the dose increases (20–40 µg/kg/min), heart rate and myocardial oxygen demand are increased along with myocardial work. In study participants with flow-limiting epicardial stenoses, intravenous dobutamine promotes an oxygen supply/demand mismatch that induces left ventricular (LV) wall motion abnormalities.

Intravenous dobutamine increases myocardial oxygen demand in a fashion similar to exercise, and thus is useful for stress testing in study participants whose exercise ability is limited as a result of peripheral vascular disease, physical incapacitation, or chronic deconditioning. Other benefits of dobutamine include its tolerance for peripheral vein infusion and its effectiveness in both perfusion and wall motion imaging.

The common side effects associated with dobutamine administration for stress include chest pain, ventricular ectopy, dyspnea, nausea, hypertension, and arrhythmias. Despite its relative safety, dobutamine is specifically contraindicated in study participants with hypertrophic obstructive cardiomyopathy, epicardial luminal narrowings of >50% in the left main coronary arterial segment, severe aortic stenosis, second- and third-degree atrioventricular block, sudden death syndrome, supraventricular tachycardia, and previous episodes of dobutamine hypersensitivity.

Although dobutamine exhibits positive inotropic activity, its chronotropic response can be suboptimal. Studies using changes in LV wall motion to identify inducible ischemia exhibit heightened sensitivity in appreciating flow-limiting epicardial luminal narrowing when the heart rate response during testing exceeds 85% of the age-predicted maximum heart rate (APMHR) response (220 − age in years). For this reason, intravenous atropine may be needed to achieve an adequate peak heart rate response during testing. Atropine is a naturally occurring alkaloid that is a competitive antagonist of muscarinic cholinergic receptors; it increases heart rate by inhibiting vagal tone. It is particularly useful in study participants taking beta-blockers, rate-limiting calcium antagonists, or those possessing a high parasympathetic drive. Atropine may be administered in increments of 0.1 to 0.3 mg, up to a total of 2 mg, to facilitate the achievement of >85% the APMHR during testing. Common side effects of atropine include dry mouth, tachycardia, and hallucinations. Abnormally high heart rates after atropine administration are best treated with intravenous beta-blockers or rate-limiting calcium channel antagonists.

Safety Profile of Dobutamine and Atropine Stress Testing

Safety is a primary concern for physicians and health care providers who administer dobutamine/atropine stress examinations. The safety profile of dobutamine/atropine stress has been reported in 6 large studies, 3 using DSE and 3 using DCMR ( Table 17.1 ). Garcia et al., Picano et al., and Geleijnse et al. reported on the adverse events associated with DSE. These were classified into major and minor complications. Major complications included death, ventricular fibrillation, sustained ventricular tachycardia, complete atrioventricular block, acute MI, rupture of the LV free wall or ventricular septal defect, transient ischemic attack, and severe hypotension. Minor complications included nausea, anxiety, and atropine poisoning with hallucinations lasting up to several hours in the absence of either myocardial ischemia or hypotension.

Across the 3 DSE studies, the rates of major and minor complications ranged from 0.1% to 4%, and 38% to 71%, respectively. Wahl et al., Kuijpers et al., and Hamilton et al. have reported on the incidence of major and minor side effects associated with DCMR. In Wahl's study of 1000 participants, 54% received atropine; in Kuijpers' study of 400 participants, none received atropine; and in Hamilton's study of 469 participants, 27% received atropine. There were no episodes of ventricular fibrillation, MI, or death during DCMR (see Table 17.1 ). The number of study participants sustaining other major events was 0.6%, 0.2%, and 0%, respectively. The percentage of participants sustaining minor events in all three studies combined was 54%. In these studies, the rates of major and minor events observed during DCMR are similar to those reported with DSE and would be expected as the dose administration is similar.

It is important to recognize that the major events are usually associated with continued administration of pharmacologic stress in the setting of concurrent myocardial ischemia. For this reason, it is important to identify ischemia promptly, and to discontinue the DCMR protocol when ischemia is recognized. In the studies reported above, many of the study participants (56%) who developed side effects had known coronary atherosclerosis and a diminished resting LV ejection fraction (LVEF). For this reason, a high level of scrutiny is used when reviewing image or ST-segment data for ischemia in the setting of reduced LVEF. Because of the risk of major adverse events, certain study participants should not receive intravenous dobutamine and atropine. Medications used for testing and emergency medications ( Table 17.2 ) for treatment of potential cardiac complications need to be readily available to improve the probability of a successful outcome should complications occur during DSE.

Dobutamine Stress Echocardiography

Since 1977, transthoracic echocardiography (TTE) has been used to acquire images before, during, and after treadmill or bicycle exercise stress, or pharmacologically induced stress. During DSE, images are acquired in four standard imaging planes: parasternal short-axis (PSAX), parasternal long-axis (PLAX), apical four-chamber (A4C), and apical two-chamber (A2C) views. The most common dobutamine infusion protocol used involves initiating dobutamine at 5 to 7.5 µg/kg/min for a period of 3 minutes, followed by 10 µg/kg/min for 3 minutes and subsequent increments of 10 µg/kg/min in 3-minute increments to a maximal dose of 50 µg/kg/min. If the patient does not achieve 85% of their APMHR, supplemental atropine is administered in 0.1 mg to 0.3 mg increments per minute (up to 2.0 mg total) until the target heart rate is reached.

Throughout the test, the four echocardiographic planes are reviewed to monitor for ischemia. During testing, LV myocardial wall motion is defined as 1 = normal, 2 = hypokinesis, 3 = akinesis, and 4 = dyskinesis. Myocardial ischemia is defined as an increase in wall motion score during testing, or the persistence of severe hypokinesis during testing. The scoring system is determined using a 17-segment model defined by the American Heart Association and American College of Cardiology. A DSE is interrupted when there is evidence of ischemia in at least two adjacent segments, severe hypertension or hypotension, dysrhythmias, unstable angina, or unexpected neurologic findings.

DSE is useful for assessing risk of future MI, death, and the need for coronary intervention. For many years, it was the modality of choice for risk stratification of cardiovascular events for patients being considered for noncardiac surgery. However, DSE is of minimal value in study participants with poor acoustic windows, often because of a large body habitus, prior cardiothoracic surgery, or pulmonary disease. In addition, there is a high interobserver variability for image interpretation; consequently, the accuracy of the test depends heavily on the proficiency of both the sonographer (acquisition) and physician (interpretation).

Dobutamine Stress Cardiovascular Magnetic Resonance

CMR is well suited to overcome the acquisition and interpretative limitations encountered during DSE. It has no acoustic window limitations and thus can obtain comprehensive visualization of the LV myocardium regardless of body habitus. In addition, image acquisition can be standardized and there is less reliance on an individual technologist's technique for acquiring high-quality images.

DCMR is commonly performed on short, 1.5 tesla (1.5 T) closed-bore systems, with bore diameters ranging from 55 to 70 cm. At the initiation of the DCMR examination, a 12-lead ECG is performed outside of the magnet. After intravenous access is established, study participants are told to lay flat on the CMR scanning table with a phased-array surface coil, brachial blood pressure cuff, pulse oximetry monitor, and respiratory gating belt attached ( Fig. 17.1 ). A physician and nurse are present throughout testing to continuously monitor the heart rate and rhythm, respiratory rate, oxygen saturation, and blood pressure. The protocol is similar to that described for DSE in that dobutamine infusions are started at 5 to 7.5 µg/kg/min, followed by 10, 20, 30, 40, and 50 µg/kg/min infusions in 3-minute stages. If study participants do not achieve 85% of their APMHR, atropine is added in 0.1 mg to 0.2 mg/min increments (up to 2 mg total) to augment the heart rate response ( Fig. 17.2 ).

Breath-hold cine balanced steady-state free precession (bSSFP) images are obtained in three apical views (horizontal, vertical, and apical long axis) and in at least three short-axis LV planes (base, middle, and apex) at each level of pharmacologic stress ( Fig. 17.3 ). If Simpson's rule is used to calculate LV volumes, short slices spanning the entire LV from base to apex can be acquired. These views are also obtained after 10 minutes of recovery to confirm that LV wall motion has returned to baseline. After the patient is removed from the magnet, the 12-lead ECG is repeated. The DCMR test is stopped if there is development of ischemia, as evidenced by a new wall motion abnormality ( Figs. 17.4 and 17.5 ): a fall in systolic blood pressure >40 mm Hg, significant ventricular arrhythmias, or achievement of the target heart rate of 85% APMHR. Although there are multiple image strategies available for the acquisition of bright-blood cine images, in general, most favor the use of bSSFP at 1.5 T, with multiple slices acquired during each breath-hold using parallel imaging techniques ( Table 17.3 ).