Late-onset prosthetic aortic valve stenosis caused by pannus formation

Abstract

Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to an open surgical aortic valve replacement (SAVR) for treating severe symptomatic aortic stenosis. Despite gaining widespread acceptance and approval for use in patients with high, moderate, and low surgical risk, the increasing use of TAVR has raised concerns about potential short- and long-term complications. We present the case of a 69-year-old female who underwent TAVR and subsequently presented to our outpatient cardiology clinic with progressively worsening dyspnea, orthopnea, and paroxysmal nocturnal dyspnea two years after the procedure. Echocardiography and stress testing revealed a recurrence of aortic stenosis, leading to a diagnosis of structural valve deterioration. The patient was subsequently scheduled for SAVR, which revealed commissural fusion, scarring, and unusual pannus formation that significantly narrowed the effective valve area, necessitating valve replacement. Despite requiring SAVR, two years after TAVR, the patient had a favorable postoperative course and outcome on follow-up. This case underscores the importance of continued surveillance and evaluation of patients who undergo TAVR, as they remain at risk for long-term complications such as structural valve deterioration. Proper management, including timely diagnosis and intervention, can lead to successful outcomes in such patients.

Learning objective

This case underscores the importance of continued surveillance and evaluation of patients who undergo transcatheter aortic valve replacement, as they remain at risk for long-term complications such as structural valve deterioration. Proper management, including timely diagnosis and intervention, can lead to successful outcomes in such patients.

Introduction

Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure for treating patients with symptomatic severe aortic stenosis (AS). It involves deploying a prosthetic valve using a catheter and serves as an alternative to open-heart surgical aortic valve replacement (SAVR). Initially approved for patients who were not the candidates for SAVR, the use of TAVR continues to expand and may eventually replace SAVR if valve durability and complication rates continue to improve. At present, TAVR is approved for patients with severe symptomatic AS at high, intermediate, and low surgical risk [1]. The most common complications of TAVR include paravalvular leak, structural valve deterioration, permanent pacemaker implantation, valve thrombosis, and stroke [2]. Structural valve deterioration, a broad category depicting any damage to the valve that may impact its function, consists predominantly of calcification, leaflet tear or failure, thrombosis, and pannus formation.

Pannus formation is described as an overgrowth of local tissue that can cause thickened cusps of the prosthetic valve and increase the likelihood of valve insufficiency and/or stenosis. Although pannus formation is believed to be less common than other structural degeneration, there are few reports describing it following TAVR. However, pannus formation is important to study as it has been noted in pathology reports, analyzing bioprosthetic TAVR valves removed due to prosthetic valve failure [3].

In this report, we present the case of a 69-year-old female who presented to the outpatient clinic two years after TAVR with progressive shortness of breath, orthopnea, and paroxysmal nocturnal dyspnea. The patient was found to have pannus formation causing stenosis of the valve, which highlights the importance of reporting on unusual instances of pannus formation that may necessitate valve replacement to understand the long-term complications of TAVR.

Case report

Two years before the current presentation, a 69-year-old woman with a medical history of paroxysmal atrial fibrillation on apixaban 5 mg twice daily, moderate AS, hypertension, hyperlipidemia, and diastolic congestive heart failure on furosemide 40 mg daily presented with shortness of breath and bilateral pitting edema in her lower extremities. She reported experiencing shortness of breath while walking around her house, which was not relieved by rest. The patient was noted to have a systolic ejection murmur with radiation to the neck, as well as trace bilateral pitting edema. The patient's troponin I levels were measured to be 0.48 ng/mL, 0.58 ng/mL, and peaked at 0.66 ng/mL. Due to the elevated troponin and significant past cardiac history, the patient underwent a left heart catheterization, which revealed no significant findings. An echocardiogram showed an ejection fraction of 55 %, a trileaflet aortic valve with moderate calcification, moderately reduced cuspal separation, and severe stenosis. The mean velocity of the aortic valve was 2.93 m/s, with a maximum velocity of 3.96 m/s, an aortic valve area (AVA) of 0.8 cm² utilizing velocity time integrals, and a mean gradient of 37 mmHg. The patient was referred to the structural heart disease clinic.

Treatment options were discussed and TAVR was ultimately chosen. The procedure was conducted without complications via a left transfemoral approach using a 23 mm Edwards SAPIEN 3 Ultra bioprosthetic valve (Edwards Lifesciences, Irvine, CA, USA). Post-operative electrocardiogram revealed normal sinus rhythm with first degree atrioventricular block. The patient was started on metoprolol tartrate 12.5 mg twice daily and continued with home dose furosemide 40 mg oral daily and apixaban 5 mg twice daily. Subsequent post operative echocardiogram results showed the peak velocity across the prosthetic valve at 2.3 m/s, AVA of 1.5 cm², and mean gradient of 13 mmHg. A repeat echocardiogram one month later revealed AVA of 1.6 cm², peak velocity at 2.9 m/s, and mean gradient of 19 mmHg.

The patient remained stable for four months but was subsequently admitted due to atrial fibrillation with rapid ventricular response (RVR) requiring cardioversion. The procedure was successful, and the patient was discharged on diltiazem 180 mg daily, and metoprolol (50 mg twice daily). Subsequent to discharge, the patient began flecainide (100 mg twice daily) for paroxysmal atrial fibrillation. The patient underwent a repeat echocardiogram one year prior to the current admission, which revealed AVA of 1.45 cm², peak velocity at 3.2 m/s, and mean gradient of 25 mmHg. Additionally, flecainide was discontinued due to the patient's reported shortness of breath and fatigue. One month after the cessation of flecainide, the patient was admitted to the emergency department due to dizziness and was found to be in atrial fibrillation with RVR. The patient elected to proceed with atrial fibrillation ablation, which was successful.

Despite the success of the initial ablation, the patient was again admitted to the hospital two months later due to atrial fibrillation with RVR. During this admission, the patient was started on amiodarone and scheduled for repeat ablation. However, during the preoperative assessment for the ablation, an expanding pericardial effusion was identified, with a maximum diameter of 2.3 cm. The pericardial effusion worsened, and a cardiothoracic surgeon opted to perform a pericardial window. Preoperatively, the patient experienced runs of atrial fibrillation, requiring parenteral amiodarone. The pericardial window was successful, and the patient was later discharged on amiodarone 200 mg daily.

Three months prior to the current admission the patient presented with increasing shortness of breath, orthopnea, and insomnia. A repeat echocardiogram showed an AVA of 1.04 cm², a peak velocity of 3.5 m/s, and a mean gradient of 33 mmHg with an ejection fraction of 75 %. Given ongoing symptoms the patient underwent a stress echocardiogram, which was stopped early due to shortness of breath. A 3D transesophageal echocardiogram was performed, showing AVA by planimetry of 1.1 cm², peak velocity at 4 m/s, and a mean gradient of 37 mmHg (Fig. 1, 3D images were not diagnostic and hence not included). The indexed AVA was 0.5 cm²/m², dimensionless index of 0.28, and acceleration time of 110 milliseconds. Given these findings, SAVR was recommended.

Fig. 1.

Evaluation of transcatheter aortic valve replacement (TAVR) valve with transesophageal echocardiogram. (a) Well-seated TAVR valve. (b) Continuous wave Doppler through TAVR valve showing peak velocity of 4 m/s.

During the surgery, the TAVR prosthetic valve was found to be degenerative, with commissural fusion and scarring (Fig. 2). Tissue examination was then performed showing dense fibrosis and dystrophic calcifications with osseous metaplasia confirmed by Van Gieson elastin and trichrome stains. Additionally, there was pannus formation at the nadir of the valve, which appeared to narrow the outflow of the valve. A root enlargement using the Nicks procedure was performed to allow for the placement of a 25 mm Edwards Inspiris Resilia pericardial tissue valve. A final transesophageal echocardiogram demonstrated that the prosthetic valve was functioning normally with a mean gradient of 10 mmHg. At follow up, the patient reported an increased functional status. A repeat echocardiogram performed three months post-operatively revealed an aortic valve peak velocity of 1.91 m/s, a mean gradient of 8 mmHg, AVA of 1.6 cm², and a dimensionless index of 0.59.

Fig. 2.

Bioprosthetic transcatheter aortic valve replacement valve after excision showing excess tissue formation near commissures and bases.

Discussion

Our patient had a unique presentation of TAVR pannus formation causing prosthetic valve stenosis. TAVR stenosis can result from various abnormalities, but thrombosis and pannus formation are the two primary causes. Thrombosis is more common, with one study reporting a prevalence of 12 % of patients with subclinical leaflet thrombosis [4] and clinical valve thrombosis has a reported prevalence of approximately 3 % [5]. In contrast, pannus formation is a less frequent complication of TAVR, and no data on its prevalence have been reported. Pannus formation refers to the growth of abnormal tissue on a prosthetic valve, leading to valve dysfunction, which can be life-threatening due to valve dehiscence, severe stenosis, or severe aortic regurgitation [6]. Symptoms can mimic ischemia and typically present with shortness of breath, chest pain, or orthopnea. In this patient, recurrent episodes of shortness of breath were the primary symptom, but she had multiple other comorbidities and hospitalizations that obscured the diagnosis of TAVR stenosis, leading to a delay in the diagnosis.

The burden of AS is substantial, affecting approximately 4.5 % of people aged 60 years and older. As of 2018, the number of worldwide patients with severe AS eligible for TAVR has increased from approximately 111,000 to 235,000 due to the expansion of TAVR to low and intermediate surgical risk patients [7]. TAVR complications include myocardial infarction, cerebrovascular events, valvular complications, arrhythmias, and vascular complications [8]. Given increased prevalence of TAVR for AS management, a multidisciplinary team needs to be educated and aware of the numerous complications that can occur.

The initial test of choice to detect valve complications is transthoracic echocardiography (TTE). TTE is used to monitor mean gradients, AVA, and peak velocity. These values enable the clinician and team to track the prosthetic valve's function. Fluoroscopy may be utilized to detect abnormalities in valve leaflet motion for mechanical valves, but it cannot definitively identify thrombus or pannus formation [9]. Although not used in this case, multidetector computed tomography (MDCT) has shown promise in distinguishing differences between pannus and thrombus using Hounsfield units. Gündüz et al. reported that if the Hounsfield units of the mass on prosthetic valve was ≥145, pannus was diagnosed with a high sensitivity and specificity in MDCT [10]. Ultimately, surgery may be required to definitively differentiate pathologically. Thrombus will appear microscopically as a fibrinous mass with erythrocytes, leukocytes, and platelets, whereas a pannus contains fibroblastic tissue along with macrophages and capillaries. Based on our tissue examination and the comparison of the imaging with clinical inspection, pannus formation is supported over thrombus due to the dense fibrotic tissue with dystrophic calcifications seen and the lack of erythrocytes, leukocytes, and platelets (Fig. 2). Treatment can vary in TAVR complications. For this patient, Fig. 1 displays the need for valve replacement; however, definitive pannus or pannus consistent cusp motion was not appreciated as later seen on the physical valve (Fig. 2). Ultimately, the decision was made to proceed with SAVR based on the worsening aortic measurements seen on the pre-operative echocardiogram and the overall clinical status of the patient. Given the need for larger size valve, aortic root expansion and definite diagnosis, our patient underwent surgical valve replacement with uncomplicated postoperative course and significant improvement in her presenting symptoms.

Conclusion

Bioprosthetic valve stenosis due to pannus formation can lead to significant morbidity and worse outcomes for patients. Early diagnosis and timely intervention with multidisciplinary team approach is crucial for favorable outcomes in this patient population.

Consent statement

Informed consent was obtained.

Declaration of competing interest

No conflict of interests exists.