Constrictive Pericarditis in a Hemodialysis Patient Who Presented with Rapidly Progressive Pericardial Calcification: A Diagnostic Challenge – A Case Report

Constrictive pericarditis (CP), a pericardial disorder, is characterized by impaired diastolic filling of the ventricles due to pericardial disease, which typically causes right heart failure with preserved right ventricular and left ventricular (LV) function [1]. A guideline article [1] describes the clinical presentation of this condition as venous congestion, hepatomegaly, pleural effusions, and ascites. In more advanced cases, hemodynamic impairment can be further aggravated by systolic dysfunction.

However, CP is usually not immediately evident on standard testing, partially because this elusive disorder may mimic other causes of heart failure or even lung or liver disease [2]. Therefore, finding a diagnostic clue may be crucial, which potentially differs among patients. In addition, CP has a diverse etiology. In developed countries, the most common reported causes are idiopathic or viral, post-cardiac surgery, post-radiation therapy, connective tissue disorder, post-infectious causes such as tuberculosis (TB), and other causes [1]. Furthermore, some literature reports, including a review article [3], have demonstrated that uremic patients develop CP. In such cases, prompt diagnosis and treatment are more crucial; otherwise, maintenance dialysis would be hampered by severe hypotension [4, 5]. We herein report a case of CP in a hemodialysis (HD) patient in a state of shock, which was clinically challenging, particularly in terms of determining a diagnosis. The patient eventually underwent surgery, which was successful. The present case may provide deep insight into the diagnosis of CP and the management of the HD population with severe hypotension [6]. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000543999).

A 53-year-old man was hospitalized in the Division of Nephrology in our facility because of severe hypotension. Fourteen years earlier, he was started on HD because of malignant hypertension. After a couple of months, he underwent a living-donor kidney transplant at a university hospital. However, after several years, dialysis therapy was resumed because of graft loss. Thus, at the time of hospitalization, he was undergoing HD 3 times weekly in a clinic close to his house. A fact that should be noted is that the failed kidney allograft was not removed because he had no established indications such as chronic graft intolerance syndrome [7]. However, approximately 2 years earlier, he had been referred to our hospital to receive hospitalization treatment for gastric ulcer. By chance, computed tomography (CT) scan revealed a number of enlarged lymph nodes in the pulmonary hila, the mediastinum, and the para-aortic region. The medical interview also revealed that, at an eye clinic, he had been diagnosed with uveitis, accompanied by visual disturbance. However, regular contact with the eye doctor was discontinued. Owing to these findings, along with elevated levels of lysozyme (29.4 μg/mL) and soluble interleukin-2 receptor (3,840 U/mL), we considered he had sarcoidosis, which required no systemic therapy such as steroid administration but only follow-up CT scans, based on the clinical diagnosis criteria published by the Ministry of Health, Labour and Welfare of Japan [8]. We attempted bronchoalveolar lavage for confirmation, but we could not obtain significant results because of an inappropriate sample material. He afterward made regular visits to a respiratory physician and ophthalmologist at our hospital every couple of months and underwent a chest CT scan semiannually. Throughout the follow-up, no findings suggested active sarcoidosis such as a lung lesion and a significant level of serum angiotensin-converting enzyme.

He very unexpectedly developed severe hypotension that eventually required oral pressor agents, despite his having a history of malignant hypertension. Shortly thereafter, right pleural effusion was detected on chest X-ray imaging (Fig. 1). Three months earlier, echocardiography was conducted with the suspicion of congestive heart failure. However, the findings did not reveal a significant cause for the pleural effusion and hypotension: pericardial effusion, undetectable; LV ejection fraction, 71%; early diastolic LV filling velocity/peak atrial filling velocity ratio, 1.49; interventricular septal thickness, 8 mm; LV posterior wall thickness, 8 mm; valves, no abnormalities.

When the patient visited our hospital to have the periodical examinations for sarcoidosis, a nurse found him nearly fainting on a bench. His blood pressure was 55/30 mm Hg, measured after resting in bed. He was immediately hospitalized in the Division of Nephrology, but the severe hypotensive state persisted. He actually often presented with presyncope, even when sitting on the bed. At the time of admission, his medications and their daily doses were as follows: 4 mg of midodrine hydrochloride and 20 mg of vonoprazan fumarate. At the time of dialysis, he also received 10 mg of amezinium metilsulfate and 10 mg of etelcalcetide hydrochloride. In addition, circulating levels of various hormones did not indicate adrenal insufficiency (cortisol, 8.24 μg/dL; adrenaline, 32 pg/mL; noradrenaline, 1,254 pg/mL; dopamine, 33 pg/mL; aldosterone, 104 pg/mL) or hypothyroidism (thyroid-stimulating hormone, 2.64 mIU/mL; free tri-iodothyronine [FT3], 2.28 pg/mL; and free thyroxine [FT4], 0.75 ng/dL). Maintenance HD was continued with some difficulty and included the intermittent use of etilefrine hydrochloride in addition to the continuous intravenous administration of dopamine hydrochloride injection. Thus, no diagnostic clue for the critical hypotension appeared at the time of hospitalization.

However, by carefully evaluating the time course of the CT images, a significant structural alteration was revealed. As shown in Figure 2, pericardial calcification had emerged approximately 1½ years earlier, and it progressed on a monthly basis. By contrast, extraskeletal calcification was sparse in other soft tissues such as blood vessels. These findings led to a presumptive diagnosis of CP. Cardiac catheterization was then conducted. Of note, right ventricular pressure studies have indicated a dip-and-plateau pattern [9], which was exactly as expected, based on our suspicion of CP (Fig. 3). Thus, a conclusive diagnosis of CP was determined.

He was transferred to a university hospital to undergo pericardiectomy. After performing a median sternotomy, the pericardium was carefully detached in conjunction with the resection of thickened parts of the pericardium. Seven pieces of the removed pericardium underwent pathological tests. The major pathological findings were fibrotic thickening of the pericardium, which otherwise lacked specific features such as sarcoidosis and infective diseases. In addition, the T-SPOT TB test (Oxford Immunotec, Oxford, UK) had a negative result. After the surgery, the blood pressure gradually became stable.

By the time he returned to the hospital 23 days after surgery, he was able to walk the length of the ward and was continuing rehabilitation and dialysis in preparation for being discharged home. He left the hospital on postoperative day 58. His dry weight had reduced by approximately 3 kg, and he resumed undergoing HD at a clinic close to his home. The pleural effusion nearly disappeared on chest X-ray imaging (Fig. 1d).

In the present case, an HD patient with life-threatening hypotension was finally diagnosed with CP and subsequently underwent successful surgery. This case was a clinical challenge, especially in regard to the diagnosis of CP and the management of severe hypotension in a HD patient.

The first diagnostic hurdle was the very limited number of clinical manifestations. Severe hypotension, followed by pleural effusion, was the only prominent feature. However, this finding may result from various other conditions. For instance, chronic hypotension, defined as a systolic blood pressure of <100 mm Hg in the interdialytic period, affects 5–10% of HD patients (and is more prevalent among patients on long-term HD) and lacks a fundamental therapy [6]. It was also consistent with the results of echocardiography that this dialysis-related complication is characterized hemodynamically by preserved cardiac stroke volume [6], further suggesting that he may have been in the terminal phase of end-stage kidney disease. Furthermore, although CP can occur after virtually any pericardial disease process [1‒3], the present case lacked a preceding episode of such conditions. This factor may be why pericardial fluid, which sometimes indicates acute or recurrent pericarditis [1], was not detected with the ultrasound procedure. In the present case, careful assessment of the progressive pericardial calcification eventually provided an important clue to the diagnosis of CP. However, extraskeletal calcification is frequently observed among patients with chronic kidney disease, owing to disturbances in mineral and bone metabolism, thereby resulting in a clinical syndrome referred to as chronic kidney disease-mineral and bone disorder [10]. In addition, a potential bias may be that CT tests were originally conducted, basically in an effort to detect lesions associated with sarcoidosis, and focused on the lungs and lymph nodes. Nevertheless, careful evaluation of the time-course changes in CT images clarified calcific lesions localized exclusively in the pericardium, which were distinctively different from those observed in patients with chronic kidney disease-mineral and bone disorder in terms of its nature of a systemic disorder [10].

The patient had several comorbidities, each of which is a potential risk factor for CP [1‒3], although histological analyses of the removed pericardium did not show anything specific to each disorder. For instance, TB remains a leading cause of CP in developing countries, whereas it is only a rare cause of CP in developed countries [1]. We paid special attention to this opportunistic infectious disease because of his history as a kidney transplant recipient [11]. However, clinical manifestations such as lung lesions were absent and the T-SPOT TB test result was negative [12]. A limited number of cases of CP related to sarcoidosis have been reported in the literature [13, 14]. In marked contrast to such reports, the patient did not present with other cardiac lesions that clearly supported an association with sarcoidosis such as the involvement of the myocardium or endocardium [13] and granulomas in the resected pericardium [14]. During the follow-up period, no significant change occurred in the serum markers of sarcoidosis such as angiotensin-converting enzyme, soluble interleukin-2 receptor, or lysozyme [8]. In light of the duration of renal replacement therapies that he had undergone, the involvement of uremia may etiologically be the ultimate differential diagnosis. In this regard, we previously reported that pericardial lesions observed in a dialysis patient may be a clinical puzzle because of the elusive nature of uremia [15]. Acute pericarditis preceded by CP [16] that was associated with uremia was also not evident in this patient. Thus, the etiology of CP remained undetermined.

The present case demonstrated that CP may mimic other disorders [2]. A multilateral approach that includes assessments of the time course and localization of lesions may provide a breakthrough for capturing this impostor.

We give special thanks to Drs. Yohei Koyashiki, Kei Aizawa, and Atsushi Kihara for their expert advice on the radiological, surgical, and pathological findings, respectively, in this study.

This study was conducted in accordance with the Declaration of Helsinki and its amendments. Ethical approval is not required for this study in accordance with national guidelines. Written informed consent was obtained from the patient for the publication of the details of their medical case and any accompanying images.

The authors declare that they have no conflicts of interest.

The authors have no funding sources to declare.

O.T., M.Y., and M.K. treated the patient and drafted the manuscript. S.T. took a central role in the patient’s treatment and revised the manuscript. K.O. collected data, including radiological images. Y.M. performed the cardiological examinations. D.N. provided a detailed review of the content and structure of the manuscript. All authors have read and approved the final manuscript.

All data that support the findings of this study are included in this article. Further inquiries can be directed to the corresponding author.