Inotropes to Differentiate Dense Spontaneous Echo Contrast From Thrombus in the Left Atrial Appendage

Excluding the left atrial appendage (LAA) thrombus in the presence of spontaneous echo contrast (SEC) is critical for percutaneous left atrial appendage closure (LAAC). After serendipitously discovering that inotrope infusion cleared dense SEC in the LAA, we used inotrope infusion in patients presenting for LAAC with SEC on preoperative transesophageal echocardiography (TEE).¹ Other groups have recently reported this strategy.² This letter details our results using this strategy to exclude LAA thrombus prior to LAAC.

This is a retrospective, multicenter study of patients presenting for LAAC from 2017 to 2019 with WATCHMAN (Boston Scientific). Patients with dense SEC on preoperative TEE received isoproterenol or dobutamine. If inotrope infusion cleared the dense SEC without residual thrombus, WATCHMAN implantation proceeded as planned. This protocol was approved by Institutional Review Boards.

Patients included had SEC stationary for ≥3 cardiac cycles or sludge.³ Patients received isoproterenol (started at 2 μg/min) or dobutamine (started at 5 μg/kg/min). Repeat TEE imaging was performed at 3-minute intervals, and the dose was increased if SEC did not resolve. Isoproterenol was increased by 2 μg/min (maximum 8 μg/min) and dobutamine was increased by 5 μg/kg/min (maximum 20 μg/kg/min). Drug infusion continued until SEC cleared or up to 12 minutes. If SEC or sludge cleared, LAAC proceeded.

Data were reviewed from procedure through 45-day postimplantation TEE for stroke and rehospitalizations. The TEE was reviewed by echocardiographic board-certified cardiologists and adjudicated by 2 independent reviewers. Continuous variables were expressed as mean ± SD and categorical variables as number (percentage). Statistical significance was assessed using paired t test for pre and peak inotrope LAA velocities. Statistical analysis was performed using GraphPad Prism 8.0.2 software (GraphPad Software). A P value ≤0.05 was used for statistical significance.

Between June 2016 and December 2019, 21 patients were identified with dense SEC on baseline intraprocedural TEE and were administered inotropes (Figures 1A and 1C). Mean age was 77.0 ± 8.5 years, 33% (n = 7 of 21) were female, mean CHA₂DS₂-VASc score was 5.4 ± 1.3, and mean HAS-BLED (hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol) score was 4.2 ± 1.0. All reported adherence to oral anticoagulation except for one intolerant to multiple anticoagulants. Congestive heart failure was present in 42.9% (n = 9 of 21), 47.6% (n = 10 of 21) had prior cerebrovascular accident, and mean ejection fraction was 49.1% ± 15.7%. Most common LAA morphology was cauliflower (66.7% [n = 14 of 21]). Dense SEC was present at baseline in 28.6% (n = 6 of 21) and sludge was present in 71.4% (n = 15 of 21).

FIGURE 1. Representative Demonstration of Dense LAA SEC Pre-LAA Closure.

(A, C) Preinotrope infusion transesophageal echocardiography (TEE) imaging of the left atrial appendage (LAA) with dense smoke. (B) Peak inotrope infusion TEE imaging of the LAA showing resolution of the dense spontaneous echo contrast (SEC) noted preinfusion. (D) Peak inotrope infusion TEE imaging of the LAA showing persistent dense SEC noted peak infusion.

A total of 17 patients received isoproterenol and 4 patients received dobutamine. SEC cleared in 19 of 21 patients (Figure 1B). Of 19 patients with SEC resolution, 6 had dense SEC, which cleared with isoproterenol (n = 5) or dobutamine (n = 1), while 13 had sludge on baseline imaging, which cleared with isoproterenol (n = 11) or dobutamine (n = 2). Two patients in whom SEC did not clear were initially categorized as having sludge on baseline TEE (Figure 1D). One was diagnosed with LAA thrombus on peak inotrope TEE and subsequently underwent cardiac transplantation, during which LAA thrombus was confirmed by direct inspection. The second patient had dense SEC diagnosed on peak inotrope TEE and underwent LAAC using a cerebral protection device.⁴

LAAC was achieved in all patients with SEC resolution except 1 with inadequate LAA depth, which was accurately measured after SEC clearance.

LAA velocities were measured by pulsed-wave Doppler pre- and peak inotrope infusion in 13 patients. LAA velocity significantly increased postinotrope infusion from 14.9 ± 8.0 cm/s to 23.1 ± 12.3 cm/s (P = 0.0063). A total of 12 of 13 patients experienced SEC clearing with peak inotrope infusion; in 4 of 12 patients, SEC cleared without change in LAA velocity. In 1 patient, SEC did not clear despite LAA velocity increasing from 11 to 24 cm/s.

No patient experienced death, stroke, systemic embolism, or device-related thrombi on follow-up. Peridevice leaks <5 mm were noted in 26.3% (5 of 19 patients) on follow-up TEE; no leaks were ≥5 mm. One patient was hospitalized at 2 weeks for delayed pericardial effusion. No clinical events were noted in 2 patients without SEC clearance.

This study highlights using ionotropic infusion to clarify presence of LAA thrombus prior to LAAC without adverse outcomes the first 45 days. Prospective studies are needed to better understand the application of inotropes and SEC in LAAC.