Correspondence *Interventional Cardiology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA

Email awilson@cvmed.stanford.edu

The case

A 28-year-old man presented at the emergency department of a hospital with acute chest pain radiating down his left arm, which had begun during vigorous exercise. His past medical history was notable for persistent paroxysmal atrial tachycardia, which had been successfully ablated 3 years earlier. Subsequent complications caused by atrioventricular block had necessitated implantation of a dual-chamber pacemaker. Transthoracic echocardiography (TTE) carried out at this time had revealed a patent foramen ovale (PFO). The patient was a nonsmoker, was not taking any medication, and had no history of cardiovascular risk factors, recent travel or immobilization, previous exertional symptoms, or family history of cardiovascular or thromboembolic disease. On physical examination, the patient's blood pressure was 130/80 mmHg, and his pulse rate was 80 beats/min, without evidence of elevated jugular pressure. No peripheral edema or rales were detected on chest auscultation.

Electrocardiography at presentation showed that the patient had an atrioventricular-paced rhythm. Cardiac enzymes were initially within normal range and the patient was admitted to hospital for further observation. He complained of ongoing chest pain, and repeat cardiac enzyme studies 6 h later showed that his level of creatine kinase had increased to 1,277 U/l (normal value 24–195 U/l), creatine kinase isoenzyme MB to 142 U/l (i.e. 11% of the patient's total creatine kinase) and cardiac troponin I to 37 g/l (normal value <0.3 g/l). No arrhythmias were documented in hospital. Serum inflammatory markers including erythrocyte sedimentation rate, C-reactive protein and white-blood-cell count were within normal range. Therapy with intravenous eptifibatide and heparin was started and the patient was also referred for urgent angiography. A thrombotic occlusion was found in the obtuse marginal branch of the left circumflex artery (Figure 1). This blood clot was successfully aspirated with a 7-French Export^® catheter (Medtronic Vascular, Inc., Santa Rosa, CA; Figures 2 and 3), with immediate resolution of the pain in the patient's chest and arm. No residual abnormalities were found in the coronary artery at the location of the thrombus or distal parts of the vessel, and the patient's thrombolysis in myocardial infarction grade 3 flow was restored. A TTE obtained after the procedure showed evidence of lateral wall hypokinesis with an ejection fraction of 40–45%, but no evidence of a pacing lead thrombus. Color Doppler ultrasonography confirmed the presence of a moderate-sized PFO with evidence of a moderate sized right-to-left shunt with Valsalva maneuver (Figure 4) and no evidence of atrial septal aneurysm or prominent eustachian valve. Subsequent histologic analysis of the clot showed evidence of a red thrombus, which was suggestive of embolism. Blood chemistry analyses showed that the patient's lipid levels were essentially normal; his fasting level of LDL cholesterol was 3.3 mmol/l, HDL cholesterol 0.98 mmol/l, triglycerides 0.76 mmol/l, and glucose 5.3 mmol/l. A thrombophilia work-up was negative, without evidence of hyperhomocysteinemia or antiphospholipid antibodies. Results from Doppler ultrasonography of the patient's lower limb and pelvic vein were normal. He was discharged from hospital 6 days later, with chronic aspirin therapy at 325 mg daily, clopidogrel therapy at 75 mg daily, and warfarin therapy aiming for an international normalized ratio of 1.5–2.5. At 6-month follow-up, the patient remained clinically well.

Figure 1 A coronary angiogram showing a coronary embolus in the obtuse marginal branch of the left circumflex artery (arrow).

 

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Figure 2 A coronary angiogram showing the obtuse marginal branch after removal of the embolus (arrow).

 

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Figure 3 Sections of clot aspirated from the left circumflex artery.

 

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Figure 4 A transthoracic echocardiogram showing a patent foramen ovale with spontaneous right-to-left blood flow (arrow).

 

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Discussion of diagnosis

Thrombosis is reported to occur with an incidence as high as 23% in patients with transvenous pacemakers and implantable cardioverter-defibrillators, and the majority of cases involve the innominate or subclavian veins.¹ Although clinical events arising from atrial or ventricular pacing lead thromboemboli are extremely rare, they are usually caused by lead-related infection.²

In the present case, a diagnosis of acute coronary syndrome was delayed because the patient was in paced rhythm at presentation, and no electrocardiographic changes diagnostic of ischemia were evident. A diagnosis was made 6 h later, on the basis of the patient's increase in cardiac enzyme levels. In retrospect, urgent echocardiography demonstrating wall motion abnormality might have been useful for making a diagnosis. Although it is possible that occult coronary artery disease caused intra-coronary thrombosis in the patient described here, intracardiac shunting of a paradoxical embolus from the pacemaker lead is a more plausible explanation. This conclusion is supported by the patient's age, onset of symptoms during strenuous exertion, his lack of cardiovascular risk factors and the angiographic appearance of the clot before and after removal, without a residual lesion in the vessel. Although no thrombus was evident on the pacing lead, the TTE was performed after the patient had received therapy with aspirin, clopidogrel, heparin and glycoprotein IIb/IIIa inhibitors, which might have led to dissolution of a residual thrombus.

Treatment and management

This case raises several management issues, including the potential use of a device for coronary embolectomy without coronary stenting, the choice of anticoagulants for prevention of recurrent embolization, and the role of PFO closure for prevention of recurrent paradoxical emboli.

In this patient, coronary embolectomy with the Export^® catheter led to immediate resolution of normal flow and the absence of residual stenosis on angiography, without the need for implantation of a coronary stent. The Export^® catheter is a component of the PercuSurge GuardWire^® distal protection system (Medtronic) and has been used as an adjunctive therapy for the treatment of thrombotic lesions in saphenous vein grafts, no-reflow during percutaneous coronary intervention, and acute myocardial infarction caused by plaque rupture thrombi (although routine use in myocardial infarction has not been shown to be beneficial).³ Other available catheters have been used to aspirate thrombi in similar clinical situations.⁴ To our knowledge, this is the first report of acute myocardial infarction caused by an embolic coronary artery occlusion, which is likely to have arisen from a pacing lead, followed by successful aspiration of the dislodged thrombus using an Export^® catheter. The decision was made not to place a stent because of the absence of residual stenosis after aspiration and the risk of restenosis after angioplasty.

As the specific etiology of the coronary occlusion in this patient was uncertain, aspirin and clopidogrel therapy was started for secondary prevention of coronary thrombi, plus warfarin because the embolus was likely to have a venous origin. Combined therapy with aspirin, a thienopyridine derivative (ticlopidine or clopidogrel) and warfarin has been associated with a slight increase in the incidence of bleeding complications. In a large population study carried out by Buresly et al.,⁵ the odds ratio for significant bleeding in elderly patients was 1.92 for a combination of aspirin and warfarin versus aspirin alone. No significant increase in risk was observed after addition of a third agent, although patient numbers in this category were small. Currently, this triple therapy regimen is most commonly used in patients treated with intracoronary stenting who have an indication for warfarin therapy, such as a prosthetic heart valve, and for stroke prevention in patients with a known, or suspected, cardiac embolic source or previous pulmonary emboli. A recent meta-analysis of patients with prosthetic valves suggests that the absolute added risk of triple-therapy regimens is small, particularly with a low aspirin dose (100 mg), and that this risk is balanced by the reduced risk of embolic events (odds ratio 0.41; P <0.001).⁶ Although the efficacy and safety of a triple-therapy regimen for the prevention of recurrent paradoxical emboli is presently unclear, it was chosen for the patient described here because the diagnosis was uncertain and warfarin therapy alone was considered inadequate for secondary prevention of coronary-plaque-related thrombotic events.

In the present case, acute coronary syndrome was attributed to a paradoxical coronary embolus, which most likely arose from the ventricular pacing lead. A PFO is estimated to be present in 25–30% of an unselected adult population.⁷ The link between the presence of PFO and systemic embolization, however, is controversial, and based largely on data that show a significantly higher incidence of PFO in young patients with cryptogenic stroke than in the general population (odds ratio 6.00).⁸ In view of the high incidence of thrombi associated with pacing leads, patients with a pacemaker and PFO might benefit from stroke prophylaxis—particularly those with an inducible right-to-left shunt.

A possible mechanism of paradoxical embolization involves a right-sided source such as venous thrombosis (including from indwelling devices), air, or amniotic fluid and reversal of a presumed left-to-right shunt that can occur with straining or during strenuous exertion. The annual risk of systemic embolic events is estimated to be increased by 3.2–3.8% in patients with PFO and documented paradoxical embolism. Although the optimum therapeutic regimen for prevention of recurrent emboli associated with a PFO has not yet been established, proposed strategies include long-term anticoagulation and surgical or percutaneous closure of the PFO. While some observational studies have shown that percutaneous closure with an atrial septal occlusion device is safe, with a low incidence of recurrent embolism, there is a lack of randomized evidence assessing this endpoint.⁹ Furthermore, recent studies using transcranial Doppler ultrasonography suggest that percutaneous closure might be associated with a higher incidence of residual shunting than surgical closure.¹⁰ Since residual shunting is linked with an increased risk of recurrent emboli, these observations could be significant.¹¹ Since aortic arch atheroma or carotid vascular disease can also lead to recurrent embolization, alternative diagnoses should be considered, particularly if events recur after PFO closure.

Conclusions

Although thrombi frequently form on transvenous pacing leads, they are rarely associated with clinical events. In the young man described here, we suspect that the coronary embolus arose from the pacing lead and was embolized via the PFO. An embolectomy catheter was used to extract the thrombus, which obviated stent placement and resulted in a good patient outcome.

Although the optimum therapeutic regimen for prevention of recurrent paradoxical emboli has not yet been determined, percutaneous PFO closure is increasingly used in this setting. Considering the high incidence of thrombi associated with pacing leads, patients with a pacemaker and a PFO might benefit from primary prophylaxis for paradoxical embolization, particularly if a significant right-to-left shunt is demonstrated.

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