Dobutamine Stress Echocardiography in End-Stage Liver Disease

Study Questions:

What is the diagnostic performance of dobutamine stress echocardiography (DSE) in end-stage liver disease (ESLD) for diagnosis of obstructive coronary artery disease (CAD), using coronary angiography as the reference standard?

Methods:

This retrospective, single-center study included patients with ESLD who underwent coronary angiography within 6 months of DSE from 2006-2017. Target heart rate for DSE was 85% age-predicted maximum heart rate, and beta-blockers were held for 3 days prior to DSE. As of 2009, atropine was added to the DSE protocol. In clinical interpretation by experienced echocardiographers, studies were considered to be indicative of ischemia at peak stress if they showed new or worsening wall motion abnormalities, reduced global left ventricular (LV) systolic function as compared to baseline, or cavity dilatation at peak stress. One investigator applied the 2007 American Society of Echocardiography guidelines for DSE and noted the presence of delayed onset or termination of contraction (tardokinesis) and lack of low-dose to peak-dose hyperkinesis as abnormal.

Because of the extended study period and improvement in equipment over time, the investigators compared DSE test performance before 2015 with that for 2015-2017. Patients were referred for coronary angiography if DSE was abnormal or equivocal or with a normal DSE in the presence of ≥1 risk factor(s) based on a practice model demonstrating a decrease in postoperative myocardial infarction and all-cause mortality after liver transplantation. Coronary angiograms were visually assessed by an experienced interventional cardiologist, and quantitative coronary angiography was performed in all patients with visual stenosis ≥40%.

Results:

Among the 633 patients included (age 59 ± 7 years, 65% male, 55% with diabetes mellitus, 57% with hypertension, 10% with prior history of CAD, 10% on statins, resting LV ejection fraction 65 ± 7%), the prevalence of CAD was 12% as defined by ≥70% stenosis in any vessel, and 17% as defined by ≥50% stenosis in any vessel. The sensitivity of DSE for ≥70% angiographic stenosis of any vessel was 24%, with specificity 90%. The combined sensitivity for positive stress electrocardiogram or echocardiogram was 28%, with specificity 86%. DSE sensitivity improved from the pre-2015 period to the 2015-2017 period (16.3% vs. 39.1%, p = 0.03).

In comparing guideline-directed interpretation to standard clinical interpretation, sensitivity was improved from 15% (9 of 60 patients) to 67% (8 of 12 patients, p < 0.001 for comparison), with a borderline-significant decrease in specificity from 94% (408 of 436 patients) to 78% (95 of 122 patients, p = 0.05 for comparison). Sensitivity of DSE in patients with LV end-diastolic diameter >4.8 cm was 38%, versus 13% in those with diameter ≤4.8 cm (p = 0.013). Independent predictors of accurate DSE results were LV end-diastolic diameter >4.8 cm (multivariate odds ratio [OR], 4.95; 95% confidence interval [CI], 1.18-20.72), statin use (OR, 7.71; 95% CI, 1.73-34.36), and interpretation based on 2007 guidelines (OR, 15.65; 95% CI, 2.85-85.19). Reaching target heart rate was not significantly associated with test accuracy (univariate OR, 1.75; p = 0.43).

Clinical follow-up was obtained for 78 patients with CAD for 19.8 ± 21.9 months. Multivessel disease was present in 36% of patients with normal DSE and 45% of patients with abnormal DSE (p = 0.42). In those who were revascularized, two underwent coronary artery bypass grafting, and 60 underwent percutaneous coronary intervention. Liver transplantation was performed in 17 patients with CAD. Cardiac events occurred in 18% of patients (10/56) with normal DSE and 45% of patients (10/22) with abnormal DSE (p = 0.01). Cardiac event-free survival was significantly shorter in those with abnormal DSE compared with those with normal DSE (mean 11.2 vs. 23.2 months, p = 0.001).

Conclusions:

In this single-center study, sensitivity of DSE for obstructive epicardial CAD in the setting of ESLD was low, but improved toward the end of the study period. DSE accuracy was greater in patients with larger LVs and in cases in which current guideline standards for DSE interpretation were applied. Abnormal DSE was associated with cardiac events among patients undergoing liver transplantation.

Perspective:

This study adds to the body of literature demonstrating that test performance of DSE in the ESLD population is suboptimal. As the prevalence of CAD in this cohort was relatively low, potential for verification bias may have been mitigated to some degree. The current findings support the idea that DSE performance is worsened in ESLD patients with small, hyperdynamic LVs. Large multicenter studies prospectively comparing methods of evaluation for myocardial ischemia in the preliver transplantation setting are needed.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Echocardiography/Ultrasound, Nuclear Imaging, Hypertension

Keywords: Atropine, Constriction, Pathologic, Coronary Angiography, Coronary Artery Disease, Diabetes Mellitus, Diagnostic Imaging, Dilatation, Echocardiography, Echocardiography, Stress, Electrocardiography, End Stage Liver Disease, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperkinesis, Hypertension, Liver Transplantation, Myocardial Infarction, Percutaneous Coronary Intervention, Risk Factors, Secondary Prevention, Stroke Volume, Ventricular Function, Left


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