Mechanical Prosthetic Aortic Valve Thrombosis Complicated by an Acute Coronary Syndrome During Fibrinolysis.

A 70-year-old man with mechanical aortic and mitral valves was admitted with progressive shortness of breath. He was found to have thrombosis of the aortic valve prosthesis. Treatment with intravenous thrombolysis was complicated by an acute coronary syndrome related to coronary embolism. The patient was successfully managed conservatively with long-term anticoagulation. An algorithm for the management of coronary embolism is suggested. (Level of Difficulty: Advanced.).

History of Presentation

A 70-year-old man with mechanical aortic and mitral valve prostheses presented to the emergency department with progressive dyspnea (New York Heart Association [NYHA] functional class III) and orthopnea over the preceding months. He denied having chest pain, palpitations, fever, or cough. He had a blood pressure of 125/80 mm Hg, a heart rate of 102 beats/min, and an oxygen saturation of 97% on 2 l of oxygen through a nasal cannula. The rest of the physical examination was remarkable for muffled S2, increased jugular venous distention, and bibasilar crackles. Medications included an oral vitamin K antagonist and aspirin.

Learning Objectives

To diagnose and understand the causes of prosthetic valve dysfunction.

To discuss the different treatment options for valve thrombosis.

To identify possible complications of thrombolytic therapy successfully.

To discuss management options for coronary embolism.

Past Medical History

The patient’s medical history was significant for hypertension, hyperlipidemia, and severe rheumatic heart disease. Three years previously, he underwent valve replacement for regurgitant lesions: 21-mm St. Jude (Abbott, Santa Clara, California) mechanical prosthetic aortic, 27-mm St. Jude mechanical prosthetic mitral valves, and a 29-mm St. Jude Attune adjustable tricuspid annular ring. Additionally, he had symptomatic heart failure, an automatic implantable cardioverter-defibrillator, atrial flutter ablation, chronic kidney disease, and chronic anemia.

Differential Diagnosis

The differential diagnosis included acute decompensated heart failure with diet and medication noncompliance, mitral or aortic prosthetic dysfunction (thrombus, pannus, dehiscence, valvular or paravalvular regurgitation), arrhythmias, infective endocarditis, acute coronary syndrome (ACS), and pneumonia.

Investigations

Laboratory studies were significant for a hemoglobin concentration of 7.7 mg/dl, a creatinine concentration of 1.38 mg/dl, and an international normalized ratio (INR) of 3.0. The transthoracic echocardiogram (TTE) showed severe prosthetic aortic valve (AV) stenosis along with moderate aortic regurgitation and moderate tricuspid regurgitation (AV mean gradient 56 mm Hg, AV peak systolic velocity 5 m/s, dimensionless valve index [DVI] 0.17, left ventricular ejection fraction 65% to 69%, mitral valve mean gradient 3 mm Hg at a heart rate of 78 beats/min) (Figures 1A and 1B). A transesophageal echocardiogram (TEE) was notable for normal prosthetic mitral valve function with normal washing jets and moderate aortic regurgitation. However, secondary to acoustic shadowing, it was unclear whether the aortic regurgitation was valvular or paravalvular. The mechanical disks were not well visualized. Cardiovascular computed tomography revealed that 1 leaflet of the AV was immobile and motion of the second leaflet was severely restricted (Figures 2A and 2B, Video 1). Additionally, a focal prosthetic valve thrombosis (PVT) was visualized (90 HU). There was no evidence of dehiscence or paravalvular leak. The mechanical mitral valve was functioning normally.

Figure 1

Transthoracic Doppler Echocardiogram

(A) Doppler echocardiogram demonstrating severe aortic valve (AV) stenosis along with moderate aortic regurgitation. (B) Doppler echocardiogram after treatment with tissue-type plasminogen activator confirming a decrease in aortic valve peak velocity.

Figure 2

Cardiac Computed Tomography

(A and B) Longitudinal and axial computed tomography images through the mechanical aortic valve with clear identification of the valve thrombus (arrows).

Management

After a discussion within the heart valve team, the patient, and his family, the decision was to treat him with fibrinolysis using 25 mg of tissue-type plasminogen activator (t-PA) over 6 h. After 10 mg of t-PA was infused, the patient experienced severe chest pain radiating to both arms. The electrocardiogram showed a paced rhythm unchanged from baseline. The infusion was stopped, and cardiac enzymes were ordered. An echocardiogram revealed new wall motion abnormalities in the left anterior descending (LAD) coronary artery territory but with improvement in mechanical AV function (AV mean gradient 17 mm Hg, AV peak velocity 3 m/s, DVI 0.3) (Figures 1A and 1B). Serum troponin peaked at 210 ng/ml on day 2. Given these findings and out of concern for coronary embolism, coronary angiography was performed and revealed a mid-LAD coronary artery embolism with Thrombolysis In Myocardial Infarction (TIMI) flow grade 2 distally, as well as a small embolism in the distal obtuse marginal coronary artery (Figure 3, Video 2). Because the patient was hemodynamically stable and blood flow distal to the lesion was seen, the operator opted for medical therapy.

Figure 3

Coronary Angiogram

Cranial anteroposterior view showing an abrupt occlusion at the left anterior descending artery with subsequent filling in the distal vessel (arrows) (Thrombolysis In Myocardial Infarction flow grade 2).

Discussion

Prosthetic heart valve obstruction can be caused by a thrombus formation, pannus ingrowth, or a combination of both (1). The initial presentation can vary from mild dyspnea to severe hypoxic respiratory failure. However, acute decline in clinical status can occur; therefore, emergency evaluation, diagnosis, and intervention can be crucial. Fibrinolytic therapy and surgical intervention remain the mainstays of treatment. Because no randomized controlled trial has compared the 2 interventions, data extrapolation from case reports, multicenter studies, and meta-analyses has been used to select 1 modality or the other depending on the clinical scenario.

The current patient has high-risk features for mechanical valve thrombosis that favor a surgical approach (Table 1) (2). These features include a NYHA functional class III and a high clot burden. Other high-risk features that were not present in our case include recurrent valve thrombosis, left atrial thrombus, or concomitant indications for an open-heart surgery (3). Despite the recommendation of the medical staff to pursue surgical mitral valve replacement, the patient opted to have thrombolysis.

Table 1

Current Guidelines for the Treatment of Left- and Right-Sided PVT

Guideline	Left-Sided PVT		Right-Sided PVT
Risk	High• NYHA functional class III to IV • Mobile thrombus • Large thrombus >0.8 cm2	Low• NYHA functional class I to II • Small thrombus <0.8 cm2 • <14 days of onset	High• NYHA functional class III to IV • Mobile thrombus • Large thrombus >0.8 cm2	Low• NYHA functional class I to II • Small thrombus <0.8 cm2 • <14 days of onset
Management	Emergency surgery	Fibrinolysis	Fibrinolysis	Fibrinolysis

NYHA = New York Heart Association; PVT = prosthetic valve thrombosis.

The optimum type, dose, and route of administration of thrombolytic agents remains unclear. Different protocols have been suggested for the treatment of PVT. In the TROIA (Comparison of Different TRansesophageal Echocardiography Guided thrOmbolytic Regimens for prosthetIc vAlve Thrombosis) trial, a single-center prospective study of 182 patients from 1993 to 2009, Ozkan et al. (4) studied multiple fibrinolytic regimens. The study compared different strategies of TEE-guided thrombolysis, which included rapid and slow infusions of streptokinase (groups I and II, respectively), high-dose (100 mg) t-PA (group III), a one-half dose (50 mg) slow infusion (6 h) of t-PA with bolus (group IV), and a low-dose slow infusion (25 mg, 6 h) without bolus (group V). Ozkan et al. (4) reported good success rates in all groups without significant differences among the groups (68.8%, 85.4%, 75%, 81.5%, and 85.5%, respectively, with a p value of 0.46). However, they noted a lower complication rate (combination of death, nonfatal major complications, and nonfatal minor complications) in group V (10.5%) compared with all other groups (p < 0.05 for each comparison). Thus, these investigators concluded that a low-dose (25 mg) slow infusion of t-PA without a bolus provides an effective and safe strategy for the management of hemodynamically stable PVT.

Ozkan et al. (5) sought to re-evaluate the findings of the TROIA trial by using a slower infusion rate in the Ultra-slow PROMETEE (PROsthetic MEchanical valve Thrombosis and the prEdictors of outcomE) trial. Ultra-slow low-dose (25 mg over 25 h) t-PA was administered to 114 patients with PVT in a single center between 2009 and 2013. The repetition of dosing was allowed up to 8 times (maximum dose of 200 mg) if needed. The valve was assessed after 12 h, and the infusion was interrupted if a TTE and TEE confirmed thrombus resolution. These investigators reported a 90% (95% CI: 0.85 to 0.95) success rate and an overall low rate of combined complications (6.7%; combined death, nonfatal major complications, and nonfatal minor complications).

As many as 3% of ACS cases are related to coronary embolism. Commonly, this embolism occurs in the setting of infective or noninfective endocarditis, cardiac tumors, or left ventricular thrombus, among other causes (6). Sources of emboli may also be paradoxical or iatrogenic. Coronary embolism is difficult to differentiate from an atherosclerotic ACS (plaque rupture/erosion).

Management of embolic ACS is different from that of atherosclerotic ACS. It is mainly dictated by the location and thrombotic burden of the embolism. In patients with high thrombus burden, aspiration thrombectomy may be a reasonable option. Routine aspiration thrombectomy in ST-segment elevation myocardial infarction does not improve cardiovascular outcomes, and it may also increase stroke rates (7,8). Conversely, no study has specifically examined embolic ACS. Intracoronary thrombolytic agents have also been used as alternative treatments (9). Our patient had a low-burden lesion with a TIMI flow grade 2 in his LAD coronary artery, along with a normal ejection fraction and no hemodynamic collapse, which led the interventionalist to opt for medical therapy (long-term anticoagulation). In the absence of specific guidelines, we propose an algorithm for the management of coronary embolism (Figure 4).

Figure 4

Suggested Algorithm for Management of Coronary Embolism

Proposed algorithm for the management of coronary emboli. IVUS = intravascular ultrasound, OCT = optical coherence tomography; TIMI = Thrombolysis In Myocardial Infarction.

Follow-Up

The patient was treated with systemic anticoagulation with unfractionated heparin followed by an oral vitamin K antagonist. His INR goal was set to be 3 to 3.5. He continued to be free of chest pain and was discharged home.

Conclusions

Thrombolysis of PVT can be complicated by ACS through direct embolization. Management should be based on the location, the thrombus burden, and the hemodynamic effects of the embolism.

Author Disclosures

Dr. Little has received institutional research support from Medtronic, Abbott, Boston Scientific, 4C, and 4Tech. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.