Author + information
- Luc A. Pierard, MD, PhD∗ ()
- ↵∗Address for correspondence:
Dr. Luc A. Pierard, Division of Cardiology, University Hospital Liege, Domaine Universitaire du Sart Tilman B35, B-4000, Liege 4000, Belgium.
- dobutamine stress echocardiogram
- end-stage liver disease
- left ventricular internal dimension at end-diastole
The number of noncardiac surgical operations represents approximately 4% of the world population per year (1). Complications occur in 7% to 11% of the procedures, the mortality rate ranges from 0.8% to 1.5%, and 42% of complications are related to a cardiac problem. It is assumed that, in the future, an increasing proportion of older adult patients with co-morbidities will be undergo surgery.
Risk stratification is mandatory. A team of experts should be considered for pre-operative evaluation of patients undergoing high-risk noncardiac surgery with known or high risk of cardiac disease. Several risk models are available, such as the modified Lee index or the National Surgical Quality Improvement Program (NSQIP) (2,3). The Lee index includes type of surgery, history of ischemic heart disease, history of heart failure, history of cerebrovascular disease, pre-operative treatment with insulin, and creatinine >2 mg/dl. The NSQIP is a risk calculator, including age, type of surgery, American Society of Anesthesiologists class, functional status, and creatinine level >1.5 mg/dl. Surgical risk depends on urgency, invasiveness, duration, and blood loss. Surgical risk estimate relies on 30-day risk of mortality or myocardial infarction; it can be low (<1%), intermediate (1% to 5%), or high (>5%).
Noninvasive cardiac imaging should be performed only in patients in whom test results indicate that management should be changed. In the European Society of Cardiology/European Society of Anesthesiology Guidelines, stress imaging is recommended (class I, level of evidence C) before high-risk surgery in patients with >2 risk factors and poor functional capacity (4). However, exercise testing is not appropriate in patients with impaired functional status due to the inability to reach the target heart rate.
Liver transplantation is considered a high-risk surgical procedure (4). It is urgent in acute liver failure and elective in most cases. The guidelines by the American Association for the Study of Liver Diseases and the American Society of Transplantation recommend cardiac evaluation with stress echocardiography as an initial screening test with cardiac catheterization as clinically indicated (Class Ib) (5). Dobutamine stress echocardiography (DSE) is widely used and validated in different clinical settings, although its accuracy is influenced by referral bias, when the result of the test (e.g., abnormal dobutamine test) affects the indication of coronary angiography (6). Classically, referral bias tends to increase the sensitivity and to decrease the specificity. Patients with end-stage liver disease (ESLD) who are candidates for liver transplantation have a small prevalence of severe coronary artery disease (CAD). Their hemodynamic characteristics include vasodilation, anemia, and high cardiac output. They are usually treated with beta-blockers to reduce the incidence of esophageal variceal bleeding. The sensitivity of DSE is highly variable, but low (32%) according to a meta-analysis (7).
In this issue of iJACC, Doytchinova et al. (8) present the accuracy of DSE in a retrospective cohort (2006 to 2017) of 633 patients with ESLD. As expected, the negative predictive value was high (90%). The specificity was 90%, and the sensitivity was only 24% despite a low prevalence (12%) of CAD, which was estimated by >70% coronary artery stenosis. The sensitivity was increased by stratifying patients into low, intermediate, and high-risk CAD groups, according to their risk factors for CAD, by considering patients with a left ventricular end-diastolic diameter of >48 mm, and by including tardokinesis and lack of hyperkinesis from low to high doses of dobutamine as abnormal.
The lack of hyperkinesis was shown to be related to a perfusion abnormality distal to a stenosis, although lack of hyperkinesis from a low to peak dobutamine dose was observed in up to 10% of patients with normal coronary arteries (9). In addition, the lack of hyperkinesis can be difficult to ascertain in patients with hyperkinesis at rest. Left ventricular (LV) regional wall thickening was shown to be heterogenous in patients with normal coronary arteries. The inclusion of this criterion may increase the sensitivity, but may be associated with a loss of specificity (9). The sensitivity of DSE was improved since January 1, 2015 to the end of the inclusion period, perhaps by recording a fifth view, the apical long-axis view, but the sensitivity was most probably improved by the use of new-generation machines. A high frame rate is required for a correct interpretation of tardokinesis.
An abnormal DSE in patients with significant CAD was associated with a higher incidence of cardiac events. Most patients (85%) underwent coronary angiography, regardless of the results of DSE. Although all patients were in ESLD, liver transplantation was performed only in 23% of patients with normal DSE and in 18% with abnormal DSE. Mean Model for End-Stage Liver Disease was 16%. A classical contraindication to liver transplantation is a MELD score of <15 (5).
The reached target heart rate was not a predictor of an accurate ischemic result, which is in contrast to a previous study that showed that the maximum heart rate achieved during DSE with the MELD score might be a predictor of adverse cardiovascular events up to 4 months post-liver transplantation (10). In the study of Doytchinova et al. (8), beta-blockers were withheld for 3 days, and pre-treatment with atropine was used during most of the study period, with additional atropine administration if needed.
False negative results have several possible explanations. Patients with ESLD have a low resting pre-load and hyperkinetic state due to their hemodynamic alterations. Dobutamine further reduces pre-load and afterload, and increases contractility with possible cavity obliteration. Peak wall stress is low; average peak rate−pressure products were 18,087 in the population of the study by Doytchinova et al. The accuracy, and, in particular, the sensitivity of DSE is lower in patients with low wall stress at a peak dose of dobutamine (11).
The investigators suggested the use of dopamine or epinephrine to increase wall stress and to improve the sensitivity of DSE in patients with ESLD. The safety and efficacy of such protocols have not yet been evaluated. Although patients with ESLD have limitations to adequate exercise, they are capable of a low charge exercise test. The combination of exercise and dobutamine test may increase peak wall stress, limit the reduction of LV dimensions, and abolish the vagal tone. The accuracy of such a protocol could be tested in a prospective study.
In summary, the prevalence of CAD is low in patients with ESLD. The sensitivity of DSE is modest. A negative test is not sufficient for predicting the absence of cardiac events during and after liver transplantation. Practically, DSE should only be performed in patients at high risk, who have at least 2 clinical risk factors of the Lee or NSQIP indexes and risk factors for coronary atherosclerosis.
Alternative techniques may be useful. Computed tomography is the ideal technique to rule out significant CAD. Stress cardiac magnetic resonance or positron emission tomography appear to be more accurate than DSE or perfusion imaging (12). Revascularization should be limited to patients exhibiting extensive inducible ischemia, such as at least 3 segments with stress echocardiography. However, revascularization does not seem to give an advantage to medical treatment even in patients with stable angina (13). New prospective studies are still needed to clarify the optimal testing method and management in many clinical settings, including patients with ESLD.
↵∗ Editorials published in the JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of iJACC or the American College of Cardiology.
Dr. Pierard has reported that he has no relationships relevant to the contents of this paper to disclose.
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