Critical exacerbation of idiopathic pulmonary fibrosis after transcatheter aortic valve implantation: Need for multidisciplinary care beyond “heart team”

Abstract

An 82-year-old man with severe aortic stenosis and idiopathic pulmonary fibrosis (IPF) underwent transcatheter aortic valve implantation (TAVI) under general anesthesia. However, following a successful TAVI procedure, he developed progressive respiratory failure because of the exacerbation of IPF. Despite the use of immunosuppressants, the patient could not be saved and he died of respiratory failure. Although TAVI is a less invasive procedure compared to conventional surgical aortic valve replacement, it is currently selected for management of severely ill, frail, and elderly patients. This case highlights the potential risk of IPF exacerbation following a TAVI procedure performed under general anesthesia.

<Learning objective: Transcatheter aortic valve implantation (TAVI) procedures have been increasingly performed for high-risk patients, including those with high frailty and pulmonary dysfunction. Although TAVI is less invasive compared to open surgery, it may cause critical exacerbation of idiopathic pulmonary fibrosis when performed under general anesthesia. Multidisciplinary care beyond “heart team” would be necessary for prevention, as well as for detecting the early signs of exacerbation of idiopathic pulmonary fibrosis.>

Introduction

Recently, there has been an increase in the number of transcatheter aortic valve implantation (TAVI) procedures. Because TAVI is a less invasive treatment compared to conventional surgical aortic valve replacement, it is selected for the management of elderly patients who present with high perioperative risks and multiple comorbidities, including high frailty and pulmonary dysfunction. Although exacerbation of idiopathic pulmonary fibrosis (IPF) has been reported in patients undergoing pulmonary or non-pulmonary surgery [1], [2], [3], few reports have described IPF exacerbation associated with TAVI [4]. We report a case demonstrating critical exacerbation of IPF after TAVI under general anesthesia.

Case report

An 82-year-old man was referred to our hospital for treatment of severe aortic stenosis with dyspnea on exertion. Based on the New York Heart Association Functional Classification, he was diagnosed as having class III heart failure. He had a history of coronary artery bypass grafting without an episode of heart failure after the operation. He had also been diagnosed as having IPF, which was based on usual interstitial pneumonia pattern found in high-resolution computed tomography (CT). Physical examination revealed dry inspiratory crackles in the bilateral lower lung fields, and auscultation of his chest revealed a systolic ejection murmur. Pulmonary function tests showed restrictive ventilatory dysfunction (forced vital capacity 62.2%, forced expiratory volume_1.0 86.5%, and carbon monoxide diffusing capacity 82.0%), without hypoxemia (oxygen saturation on room air 98%). Arterial blood gas examination on room air showed the partial oxygen pressure of 93.5 mmHg (P/F ratio 445) and the partial carbon dioxide pressure of 45.2 mmHg without acidemia (pH 7.426). Chest CT confirmed reticulation and honeycombing prominent in the bilateral dorsal and lower lung fields (Fig. 1). Laboratory data did not indicate active IPF (Table 1). We confirmed no findings indicating secondary interstitial pneumonia complicated with collagen diseases, including elevation in rheumatoid factor, anti-nuclear antibodies, and anti-neutrophil cytoplasmic antibody. Echocardiography showed normal left ventricular ejection fraction with severe aortic stenosis without pulmonary hypertension.

Fig. 1.

Chest thin-slice computed tomography before transcatheter aortic valve implantation. Chest thin-slice computed tomography confirmed reticulation and honeycombing in the bilateral dorsal and lower lung fields, which was consistent with usual interstitial pneumonia pattern of baseline idiopathic pulmonary fibrosis.

Table 1.

Laboratory data before transcatheter aortic valve implantation (TAVI) and at re-admission.

	Before TAVI	At re-admission
Complete blood cell counts
White blood cell (μL)	4400	10,000
Neutrophils (%)	80.1	88.2
Lymphocytes (%)	9.8	6.9
Monocytes (%)	7.5	4.5
Eosinophils (%)	2.2	0.2
Basophils (%)	0.4	0.2
Red blood cell (104/μL)	321	318
Hemoglobin (g/dL)	10.1	9.6
Hematocrit (%)	31.5	30.9
Platelet (104/μL)	16.3	13.4
Blood chemistry
Aspartate transaminase (IU/L)	18	233
Alanine transaminase (IU/L)	12	193
Total bilirubin (mg/dL)	0.6	0.6
Lactate dehydrogenase (IU/L)	166	994
Sodium (mEq/dL)	140	140
Potassium (mEq/dL)	4.1	4.1
Chloride (mEq/dL)	102	106
Blood urea nitrogen (mg/dL)	31.0	37.8
Creatinine (mg/dL)	1.86	2.15
Total protein (g/dL)	5.5	6.9
Albumin (g/dL)	3.1	3.0
C-reactive protein (mg/dL)	0.13	12.68
Krebs von den lungen-6 (U/mL)	438	1942
Surfactant protein-D (ng/mL)	193	435
Brain natriuretic peptide (pg/dL)	560	709

He underwent TAVI under general anesthesia, which was maintained with continuous intravenous infusion of remifentanil and inhalation of sevoflurane. Intraoperative oxygenation was well maintained with a tidal volume of 5.3–8.3 mL/kg, fraction of inspired oxygen of approximately 40%, and peak airway pressure <15 mmHg. A prosthetic aortic valve (CoreValve™ 29 mm, Medtronic Inc., Minneapolis, MN, USA) was successfully implanted via a transfemoral approach. Anesthesia time was 181 min. The patient demonstrated a smooth recovery from anesthesia, and he was extubated immediately after the operation. Although in/out balance was +440 mL during the procedure, hemodynamic status had been stabilized, as evident in a left ventricular end-diastolic pressure of 8 mmHg and central venous pressure of 8 mmHg during the procedure. Body weight was not increased immediately after the procedure, and postoperative echocardiography confirmed euvolemic status. Blood gas analysis after extubation showed adequate oxygenation. Temporary right ventricular pacing was maintained after TAVI because he developed a transient complete atrioventricular block.

On postoperative day (POD) 14, he developed dyspnea and cough, and chest auscultation revealed aggravation of inspiratory crackles in the bilateral lung fields. Serum levels of brain natriuretic peptide (BNP) and Krebs von den lungen-6 (KL-6) were elevated postoperatively compared to preoperative values (Fig. 2). Serum β-d-glucan was <3 pg/dL and the cytomegalovirus antigen was negative. Laboratory data showed exacerbation of inflammation (C-reactive protein 8.2 mg/dL). On POD 16, he underwent bronchoalveolar lavage (BAL), which demonstrated no specific findings without elevation in cell counts of neutrophils, lymphocytes, and eosinophils. Cultures obtained from BAL specimens, sputum, urine, and blood yielded negative results. Echocardiographic findings were consistent with congestive heart failure with preserved ejection fraction (60%), showing elevated left atrial pressure and central venous pressure. Aortic stenosis had been cured with no findings of transvalvular or paravalvular leakage. CT confirmed development of new ground-glass opacities in the bilateral lungs (Fig. 2). Based on these findings, he was treated for congestive heart failure associated with diastolic dysfunction, mitral regurgitation, a transient complete atrioventricular block, and frequent episodes of paroxysmal atrial fibrillation observed after TAVI. Following treatment of congestive heart failure, his dyspnea improved with a decrease in BNP. Echocardiography confirmed hemodynamic improvement. He underwent permanent pacemaker implantation on POD 38 after stabilization of his respiratory status. Although KL-6 level kept elevating and peripheral reticulation remained even after the improvement in bilateral ground-glass opacities on POD 60 (Fig. 2), his respiratory symptom had been stabilized without a re-increase in BNP as well as lactate dehydrogenase levels. He was discharged on POD 62. However, he was re-admitted on POD 70 for complaints of dyspnea, cough, and fever. Upon re-admission, echocardiographic findings did not indicate worsening of left heart failure. KL-6 and lactate dehydrogenase levels were further elevated compared to values noted at the time of discharge. Arterial blood gas examination under oxygen inhalation showed exacerbation of oxygenation (partial pressure of arterial oxygen 84.8 mmHg, P/F ratio 106). Laboratory data showed an exacerbation of inflammation (Table 1). Serum β-d-glucan, procalcitonin, and blood and sputum cultures were negative. Chest radiography and CT showed the appearance of newly developed diffuse ground-glass opacities in the bilateral lungs (Fig. 2). Based on these findings, specific complication including bacterial or aspiration pneumonia was unlikely, then he was diagnosed as having exacerbation of IPF and immediate treatment was initiated. He was administered high-dose methylprednisolone pulse therapy (1 g daily for 3 days) with supportive non-invasive positive pressure ventilation, followed by oral administration of prednisolone at a daily dose of 50 mg. A BAL was repeated, but again demonstrated no specific findings, and results of culture were also negative. He died of respiratory failure on POD 105. Autopsy could not be performed.

Fig. 2.

Chest radiography and thin-slice computed tomography evaluation findings with laboratory data and echocardiographic findings. Ground-glass opacities in the bilateral lungs with elevated tricuspid regurgitation pressure gradient (TRPG) and E-wave velocity were detected on postoperative day (POD) 14. Following treatment of congestive heart failure, computed tomography (CT) showed improvement in ground-glass opacities with residual reticulation on POD 60, along with a temporal decrease in brain natriuretic peptide (BNP) level and improvement in echocardiographic findings. On POD 70, development of new diffuse ground-glass opacities was seen in the bilateral lung fields without evidence of left heart failure, which was diagnosed as an exacerbation of idiopathic pulmonary fibrosis. Re-elevation of BNP level and TRPG on POD 70 were consistent with right ventricular overload and pulmonary hypertension due to exacerbation of idiopathic pulmonary fibrosis. Note consistent and progressive increase in Krebs von den lungen-6 (KL-6).

CRP, C-reactive protein; LDH, lactate dehydrogenase; TAVI, transcatheter aortic valve implantation.

Discussion

The incidence of periprocedural IPF exacerbation was reported to be 0.4% among patients undergoing TAVI [4]. It is important to focus on specific populations with a baseline interstitial lung abnormality, which was found in 14.7% of those referred for TAVI [5]. These data suggest that IPF exacerbation will occur in 2–3% of TAVI cases with a baseline interstitial lung abnormality. This is consistent with previous reports that postoperative exacerbation of IPF has been observed in 2–14% of patients with IPF who had undergone pulmonary or non-pulmonary surgery [1], [2], [3].

As shown in our case, the progressive and latent exacerbation of IPF can be masked by concomitant left heart failure. Following the treatment of heart failure, ground-glass opacities as well as lactate dehydrogenase level temporarily improved, indicating the difficulties of using these signs as a marker specific for IPF. Also, BNP level can be elevated in the setting of exacerbation of IPF due to right ventricular pressure overload [6]. Only KL-6 showed continuous elevation, which was a useful biomarker for diagnosis of IPF [7]. A consistent increase in KL-6 levels would have indicated latent exacerbation of IPF at least two weeks after TAVI (Fig. 2), which was masked by concomitant heart failure. As shown in our case, IPF exacerbates several weeks following the triggering event [1].

Intraoperative respiratory management under general anesthesia including mechanical ventilation with high tidal volume or high concentration oxygen supplementation are predisposing factors for postoperative exacerbation of IPF [1]. Alveolar overstretching or alveolar shear stress promotes inflammatory mediators, and induces local alveolar or systemic inflammation, as well as high oxidative stress [8]. Therefore, a lung protection strategy avoiding high tidal volume and high fraction of inhaled oxygen is selected to prevent postoperative pulmonary complications [8]. Although management of our patient’s respiratory status, including use of general anesthesia was based on standard lung protection strategy, a further reduction in tidal volume and oxygen supplementation could be considered to prevent IPF exacerbation. Although the role is controversial, perioperative use of pirfenidone or glucocorticoids have been suggested to reduce the potential risk of postoperative exacerbation of IPF [9], [10]. In addition to general anesthesia with mechanical ventilation, BAL by itself, lower body mass index, and baseline pulmonary dysfunction (a low forced vital capacity, a low carbon monoxide diffusing capacity, and poor baseline oxygenation) have shown an association with an exacerbation of IPF [9], [11]. In our case, general anesthesia with mechanical ventilation, lower body mass index (21.7 kg/m²), and a low forced vital capacity were presumably the risk factors associated with IPF exacerbation. If anything associated with general anesthesia, including mechanical ventilation, intraoperative medications, and larger periprocedural stresses should surely be an inducer of IPF exacerbation, TAVI under local anesthesia would be an attractive option [12].

TAVI is preferred over a surgical aortic valve replacement in patients with severe aortic stenosis and/or those with high-risk comorbidities, including pulmonary dysfunction [13]. Although TAVI is less invasive compared to open surgery, our case showed that IPF exacerbation could be induced even after TAVI. When IPF exacerbation occurs, the mortality was as high as appropriately 46% even if the above-mentioned therapeutic interventions are used [9]. It must be borne in mind that compared to conventional surgical candidates, recently, a greater number of seriously ill elderly patients undergo the TAVI procedure. The potential risks of a procedure with general anesthesia in this geriatric population should not be regarded as similar to those observed in conventional populations. Further investigation is necessary to identify the factors associated with IPF exacerbation in these critically ill patients and to determine suitable prevention strategies. As the baseline interstitial lung abnormality is independently associated with an increased risk of mortality in the TAVI population [5], careful evaluation of the preprocedural lung CT and respiratory function is also important, even if the lesion is not extensive, as in the present case. Furthermore, careful perioperative monitoring and a multidisciplinary approach beyond so-called “heart team”, would be necessary to detect early signs of IPF exacerbation.

Conflicts of interest

The authors declare no conflicts of interest in association with the present study.