A simultaneous occurrence of pulmonary embolism and cerebral infarction following Micra™ leadless pacemaker implantation

Since the successful implantation of the first cardiac pacemaker (PM) in 1958, PM has been widely used in clinical practice. With the advancement of interventional technology, PMs have become smaller and more effective. Despite continuous improvements, traditional PMs remain associated with a proportional risk of immediate- and short-term complications (9%–12%),^[1] which are mainly related to electrodes or pockets. Short-term complications include pneumothorax, cardiac tamponade, electrode dislodgement, and pocket hematoma,^[2] while long-term complications include tricuspid regurgitation, venous obstruction, lead fractures, insulation failure, and device-related infection.^[3]

In contrast, compared with that of the conventional PM, a leadless pacemaker (LP) is a promising pacing system that can prevent pocket- and electrode-related complications.^[4] The LP is a capsule-like device that is placed in the right ventricle, usually at the interventricular septum.^[5] For instance, the Micra™ transcatheter leadless pacing system has demonstrated high procedural success rates (90%–95%) in several large-scale clinical studies.^[6] Nonetheless, there are potential risks of complications for the LP system, such as vascular damage, cardiac perforation, pericardial effusion, high capture thresholds, and ventricular arrhythmia.^[7] Herein, we reported an extremely rare but potentially fatal complication of pulmonary embolism coexisting with cerebellar infarction, which was found to be caused by a paradoxical emboli through the patent foramen ovale (PFO).

An 85-year-old man with a history of moderate renal insufficiency was admitted with recurrent amaurosis and syncope, with each episode lasting from a few tens of seconds to several minutes. His electrocardiogram showed first-degree atrioventricular block (AVB) (Figure 1A), and Holter monitoring showed transient third-degree AVB with the longest RR interval of 3.1 s (Figure 1B). He had hemoglobin of 128 g/L (normal range: > 120 g/L), serum potassium of 4.3 mmol/L (normal range: 3.5–5.5 mmol/L), hypersensitive troponin I of 0.005 ng/mL (normal range: < 0.03 ng/mL), serum D-dimer level of 0.46 mg/L (normal range: < 0.5 mg/L) and normal level of thyroid function. He was in chronic kidney disease of stage 3 with serum creatinine of 1.72 mg/dL (normal range: < 1.2 mg/dL) and glomerular filtration rate of 34.9 mL/min (normal range: > 80 mL/min). His echocardiogram showed normal cardiac structure and function. Head computed tomography examination was normal without the sigh of acute stroke. He hadn’t taken any antiarrhythmic medicine. After excluding these underlying etiologies of syncope, the patient’s episode was due to intermittent high degree AVB. Considering the old age and non-pacemaker dependence of the patient, we recommended the patient have a LP implanted for preventing pocket- and lead-related complications. The patient underwent percutaneous implantation of Micra™ LP at the right ventricular septum through the right femoral vein. We routinely injected heparin intravenously (50 U/Kg) during the operation to prevent thrombosis. The electrical testing of the device demonstrated the R-wave sensing value of 5.8 mV, impedance of 658 Ω, and pacing threshold of 0.75 V at 0.24 ms. The puncture site of the right femoral vein was approximately 1 cm and was sutured with an internal “8-figure” suture without hematoma and lower limb swelling. The patient recovered without complications and was discharged on the third post-operative day, with a recommendation for follow-up.

Figure 1.

Baseline electrocardiogram: first-degree atrioventricular block (A), and Holter: transient high-grade atrioventricular block with the longest RR interval of 3.1 s (B).

One month later, the patient experienced a syncope recurrence, which lasted several minutes. He began to speak slackly and walked unsteadily, and was subsequently re-admitted to our hospital. His vital parameters were within normal limits; however, his SpO₂ was 93% on room air. Laboratory evaluation revealed a serum D-dimer level of 16 mg/L, serum creatinine of 1.79 mg/dL and glomerular filtration rate of 33.5 mL/min. Micra™ interrogation showed normal device function with intermittent pacing and stable sensing, impedance, and pacing threshold values without tachycardia or bradycardia events. Pulmonary artery computed tomography angiography scan confirmed an acute bilateral pulmonary embolism in the lobar, segmental, and subsegmental branches (Figure 2A–2D). Magnetic resonance scan of the head revealed a fresh infarction in the left cerebellar hemisphere and a sporadic ischemic focus in the bilateral oval and subfrontal cortices (Figure 3). Vascular ultrasonography of the bilateral lower extremities revealed normal venous flow without thrombosis. Based on the relevant examination results, malignant tumors and autoimmune diseases were excluded. Moreover, a PFO was detected by transesophageal echocardiography in this patient, and his bubble test was positive.

Figure 2.

Pulmonary artery computed tomography angiography showing bilateral pulmonary embolism in the lobar, segmental, and subsegmental branches (A–D).

The shadow in the pulmonary artery indicated by the arrow was the thrombus.

Figure 3.

Magnetic resonance scan of the head demonstrating a fresh infarction in the left cerebellar hemisphere.

The brightening area of the cerebellum indicated by the arrow was the infarct.

Low molecular weight heparin (enoxaparin, made by Sanofi) for anticoagulation was administered 4000 IU twice a day for 14 days. The patient’s symptoms of slurred speech and unsteady walking improved gradually without bleeding complications. His SpO₂ increased to 98% on room air, and the serum D-dimer level decreased to 2.64 mg/L. Re-examination of the thoracic computed tomographic angiography indicated that the pulmonary vascular thrombosis had completely disappeared (Figure 4A & 4B). Thus, antithrombotic regimen was adjusted to 15 mg of oral rivaroxaban once daily for long-term application. The patient was discharged successfully, and no discomfort symptoms, such as chest breathlessness and syncope, were observed during the 12-month follow-up period.

Figure 4.

Thoracic computed tomography angiography of the chest showing that the bilateral pulmonary embolism has completely disappeared after antithrombotic therapy (A & B).

Recently, LPs have become an alternative strategy to conventional transvenous PMs, which effectively prevents complications associated with leads and pockets. A multicenter cohort and post-approval registry of Micra™ LP has reported high implantation success rates (> 99%) with long-term stability of electrical performance and long-term safety.^[8] In a real-world study of United States Medicare patients, the Micra™ leadless VVI PM was associated with a 38% lower adjusted rate of reinterventions and 31% lower adjusted rate of chronic complications compared with those of transvenous VVI PMs.^[9] Darlington, et al.^[10] reported that a total of 18 studies were included with 2496 patients implanted with a LP and success rates range between 95.5% and 100%. The device or procedure related death rate was 0.3% while any complication and pericardial tamponade occurred in 3.1% and 1.4% of patients, respectively. Vincent, et al.^[11] analyzed the data of single-chamber LP implantation in 2016 in the United States. Compared to transvenous PM, LP implantation was associated with lower complication rates (8.6% vs. 11.2%) but greater mortality (5.2% vs. 1.3%, P < 0.001).

Despite the high surgical success rate and extremely low rate of complications associated with LP, there is still a need to remain vigilant on surgical-related adverse events. In the Investigational Device Exemption study, complications were recorded in 4% of the patients, including venous thrombosis (0.3%), vascular complications (0.7%), and cardiac perforation (1.6%).^[9] Moreover, in the LEADLESS II trial, 20 patients (6.7%) experienced adverse events including cardiac perforation (1.3%), device dislodgement (1.7%), elevated pacing thresholds requiring retrieval and replacement (1.3%), and vascular complications (1.3%).^[12] Ranka, et al.^[13] has recently reported a case of systemic embolism after the placement of the Micra™ PM. Radiographic imaging incidentally discovered that the LP was inadvertently lodged in the lateral wall of the left ventricle.

This case report described a severe complication of simultaneous pulmonary embolism and cerebellar infarction after a Micra™ LP implantation. In general, common risk factors for pulmonary infarction include long-term bed rest, obesity, physical trauma, recent abdominal or lower limb surgery, and malignant tumors. Early mobilization is recommended for patients after Micra™ implantation to prevent the formation of deep venous thrombosis in lower limbs. In our center, patients can get out of bed 6 h after surgery. Lower extremity vascular ultrasound and subcutaneous injection low molecular weight heparin are not routinely recommended unless the patient has evidence of deep venous thrombosis in the lower extremity. The embolus of a cardiogenic cerebral infarction may come from the left atrial appendage or from a systemic circulation embolus with a right-to-left shunt. The patient had no previous history of atrial fibrillation. He had cerebral infarction and pulmonary infarction simultaneously, and he had right-to-left shunt via PFO. Therefore, we believed that the emboli of cerebral infarction was more likely to come from systemic circulation.

The rare complication in the present case may be due to PFO-related abnormal embolism, resulting in a right-to-left shunt of venous thrombosis and cerebellar artery occlusion. The patient was not physically active and preferred to sit or lie down because of old age and comorbidities. Further, the possibility of blood hypercoagulability caused by tumors and autoimmune diseases was also excluded. Although there was no obvious deep venous thrombosis in the patient’s lower extremities detected by the ultrasound examination, the puncture site of the right femoral vein was relatively long (approximately 1–2 cm), and coupled with his lack of exercise, could have led to the right lower extremity thrombosis. Moreover, considering the patient’s old age and history of renal insufficiency, we reduced the dose of low molecular weight heparin appropriately. Fortunately, the pulmonary thrombosis of the patient completely resolved without the occurrence of a bleeding event after two weeks of anticoagulation treatment.

This is the first report of a severe complication of a simultaneous occurrence of pulmonary embolism and cerebellar infarction following a Micra™ LP implantation, which was caused by a paradoxical embolism associated with PFO. Notably, if patients are in a hypercoagulable state, early post-operative activity and anticoagulant therapy may be recommended after a Micra™ LP implantation. Moreover, transcatheter closure of the PFO is recommended for young and middle-aged patients with hemicrania or stroke caused by paradoxical embolisms.