Granulomatosis polyangiitis of the heart—an unusual presentation: a case report and review of literature

Abstract

Granulomatosis with polyangiitis (GPA) is a multi-system disorder associated with ocular, renal, cardiac, pulmonary involvement. However cardiac involvement is very rare compared to other systems. We present a case of an unusual presentation of GPA associated with ocular involvement super imposed on pre-existing rheumatic valvular disease. The cardiac involvement manifested as a thick fibro elastic membrane encasing the aortic and mitral valve annuli making the valve replacements a real technical challenge. The patient needed permanent pacemaker implantation due to intermittent complete heart block that was present even preoperatively. The patient was started on steroids and is doing well until the last follow-up. This case highlights the importance of recognition of GPA in cardiac surgery and to be aware of such an entity when one encounters a thick whitish avascular fibro elastic membrane encasing cardiac valves and endocardium, obliterating the anatomical delineation of structures during surgery.

Introduction

Connective tissue disorders always have a myriad of presentations with every case being an enigma in itself. Granulomatosis with polyangiitis (GPA) is no such exception to this. Herein, we discuss a very rare and interesting association of rheumatic heart disease (RHD) and GPA presenting as a fibro elastic membrane posing a technical challenge during valve replacement surgery. The suspicion of GPA should warn the surgeon of possible technical difficulties during surgery and plan accordingly.

Case report

A 44-year-old normotensive, euglycemic female, known with RHD, underwent closed mitral commissurotomy (CMC) at the age of 25 years for severe mitral stenosis and was on regular follow-up with a cardiologist. She was also diagnosed with right eye necrotizing scleritis by an ophthalmologist six months before and was on prednisolone 0.12% eye drops for the same. She had a history of epistaxis intermittently. She presented to our cardiology department with dyspnea on exertion for the past 2 months. On presentation, she was breathless with a heart rate of 45/min, blood pressure of 90/60 mm Hg, a saturation of 95% with 15 l of O₂/min by face mask. Her Electrocardiogram showed a complete heart block (CHB) with a ventricular rate of 45/min. Her chest X-ray anteroposterior view showed cardiomegaly with increased broncho vascular markings in bilateral lung fields. Temporary pacing was initiated through right internal jugular venous access and she was stabilized with Inj. dobutamine 5 mic/kg.min. Her blood investigations showed a total white blood cell count of 8000 cells/cumm and an elevated erythrocyte sedimentation rate (ESR) of 76 mm/h. On echocardiography, the patient had severe mitral restenosis (Fig. 1a), moderate aortic stenosis with moderate aortic regurgitation (Fig. 1b) with a small annulus (19 mm), severe pulmonary artery hypertension (PAH) (75 mm Hg), and preserved biventricular function. Preoperative coronary angiogram showed normal coronaries. After a couple of days, her own heart rate improved and she returned back to sinus rhythm with a prolonged PR interval (no rate-limiting drugs) of 220 ms with stable hemodynamics. She was planned for a double valve replacement (aortic and mitral).

Fig. 1.

a Parasternal short-axis 2D echo view showing thickened stenotic mitral valve leaflets. b Parasternal long axis 2D echo view showing aortic regurgitation jet

Through a median sternotomy and after releasing the adhesions due to previous CMC, cardiopulmonary bypass (CPB) was established by aorto-bicaval cannulation. After achieving blood cardioplegic arrest, the left atrium (LA) was opened by developing the interatrial groove. In spite of the enlarged LA, the exposure of the mitral valve was extremely difficult. We visualized the mitral orifice and there was a thick whitish glistening membranous structure occupying the entire area of the mitral valve and LA endocardium. The anatomical distinction was difficult to delineate between the mitral annulus and surrounding structures. A vertical cut along the 12 o’clock position of the anterior mitral leaflet (AML) along with circumferential excision in small elliptic tissues was the only way to increase the mitral valve orifice (MVO). In the absence of anatomic delineation and poor visibility, the leaflet was excised slowly and carefully. This problem was compounded further by the thick membrane involving the left ventricle (LV) endomyocardium as well. We could not identify even papillary muscles in LV cavity. After defining an imaginary mitral annulus and after excision of tissues around mitral orifice and creating room in LV cavity by excising membranous tissue from LV cavity, a 25-mm mechanical bileaflet (St. Jude Medical) could be seated with difficulty in mitral position using 2–0 polyester braided sutures by interrupted pledgetted technique with pledgets placed on the LV side. After mitral valve replacement (MVR), a transverse aortotomy was done and the trileaflet aortic valve leaflets were excised and aortic annular calcium was carefully debrided. Aortic valve replacement was done with a 19-mm mechanical bileaflet valve (St. Jude Medical Regent) with sutures along the non-coronary sinus placed supra annularly using interrupted non-pledgetted suturing technique. The aortic cross-clamp time was 193 min and CPB time was 223 min. The excised mitral and aortic valve leaflets along with fibro elastic membrane (Fig. 2) were sent for histopathological examination. The patient was weaned off CPB with ventricular pacing back up of 80/ min (as her own rhythm was junctional with heart rate of 50/min) with Inj. dobutamine 5 mcg/kg/min and Inj adrenaline 0.05 mcg/kg/min. The transesophageal echo showed normal functioning of both the valve leaflets with no paravalvular leak. She was extubated the next day and was gradually weaned off inotropes and was in intermittent CHB requiring pacing through temporary epicardial ventricular pacing. She was discharged to the ward on 3^rd post-operative day (POD) with pacing backup. As there was intermittent CHB even on the 7^th POD, she underwent permanent pacemaker implantation (PPI). The histopathology report of the aortic valve leaflets showed extensive areas of necrosis characterized by neutrophilic central suppuration and peripheral palisading granuloma (which differentiates it from other connective tissue disorders) including multi-nucleated giant cells (Fig. 3a) suggestive of GPA. The mitral valve showed only postinflammatory changes (Fig. 3b) suggestive of RHD with no evidence of GPA. This was a real surprise for us and a rheumatologist opinion was obtained. On his suggestion, the cytoplasmic (C) and perinuclear (P) anti-neutrophilic cytoplasmic antibodies (ANCA) were sent which were negative (immunoblotting technique). The urine protein creatinine ratio was also normal (0.05) indicating no renal involvement as of now. Computed tomography (CT) of the chest was done to look for any pulmonary involvement which came negative though. She was diagnosed with a limited GPA as per the 2017 American College of Rheumatology (ACR) criteria which in our case includes ocular involvement with necrotizing scleritis, epistaxis, and cardiac involvement (positive biopsy finding). She was treated with steroids Tab prednisolone 30 mg/day with weekly tapering of 5 mg/ week for a total of 6 weeks. She was discharged in a clinically stable condition on warfarin with an international normalized ratio (INR) of 3.5. She is on regular follow-up with rheumatologist and cardiologist. On the last follow-up at 2 months post-surgery, she is in New York Heart Association (NYHA) class I with echo showing normal mechanical prosthetic valve function, no paravalvular leak, with mean gradients of 5 mm Hg and 17 mm Hg at mitral and aortic positions respectively with left ventricular ejection fraction (LVEF) of 50% and a moderate PAH (50 mm Hg).

Fig. 2.

Pathology specimen showing thickened fibro elastic membrane that was excised during mitral valve replacement

Fig. 3.

a Aortic valve histology (× 40)—palisading granuloma, central suppuration (bottom two arrows) and top arrow—multinucleated giant cell (GPA)—hematoxylin eosin (HE) stain. b Mitral valve (× 10)—(black arrow) rheumatic laminar fibrosis—HE stain

Discussion

GPA (formerly Wegener’s granulomatosis) is a type of vasculitis that is most of the time associated with diffuse anti-neutrophil cytoplasmic antibodies (cANCA). The upper and lower airways and the kidneys are the usual organs affected by it. Cardiac involvement in GPA is rare (6–12%) but if found, the mortality increases to 25% [1]. The cardiac involvement may present in many forms like conduction abnormalities, inflammation of the endocardium, myocardium, pericardium, cardiac valves, and coronary arteries, and in some cases, it may also result in aneurysms of the aorta and myocardial infarction. In a study by Morelli et al., three (out of eight patients with GPA in total) had aortic involvement by GPA, needing valve replacement [2]. There also has been an anecdotal report of a female with GPA with third-degree heart block, needing pacemaker implantation [3]. A case report of valvular GPA has also been published wherein there was a mass lesion of the mitral valve [4]. Very rarely coronary artery thromboembolism [5] has been reported. Ruisi et al. describe in their review about 20 case reports that have been documented to show either the aortic or mitral valve showing features of GPA either pathologically or clinically [6]. It is a rare entity which when diagnosed early can lead to proper treatment and better outcomes for the patient.

Positive ANCA serology is not necessary for establishing a diagnosis of GPA [7] provided clinical and biopsy-proven points favor the diagnosis of GPA as in our case. The reasons for negative ANCA serology in certain patients still remain an enigma.

The special features in our patient which make it unique when compared to other case reports are summarized below:

1. Combined affliction of GPA and rheumatic valvular heart disease

2. Cardiac valvular involvement of GPA in the form of fibro elastic membrane rather than as a mass which is usually the case as reported by anecdotal literary reviews

3. Absence of pulmonary involvement in a biopsy-proven GPA

Once the diagnosis of GPA is established, it needs prompt treatment with steroids and immunomodulators based on the disease activity and the number of systems involved [7]. In our case, it was the cardiac and the ocular system involvement that needed steroid treatment.

One of the most important differential diagnoses of GPA is infective endocarditis (IE). IE presents with fever, demonstrable vegetations on echo in the mitral and aortic valves, and blood culture growing organisms most commonly staphylococcus or streptococcus. Usually, the response to antibiotics is quite phenomenal in IE while GPA on the contrary is culture-negative and ANCA-positive and response to steroids is quite dramatic. Though there can be overlap amongst the two spectra of diseases, biopsy of the involved organs is always diagnostic to have a clear differentiation between the two [8].

Theoretically, there is a possibility that due to the disease activity of GPA, implanting a pacemaker with the right ventricle (RV) might pose a problem regarding the voltage sensitivities and thresholds. We suspected an ongoing inflammatory process in the RV too just like what happened in LV. However, this did not happen in our case and as well as in the anecdotal report [4] implying that there must be a long latent period for the RV endocardium to get involved affecting the pacemaker thresholds.

There are no clear-cut features on echo which might help to differentiate quantitatively and qualitatively between LA clot, wall thickening, or fibro elastic membrane as all these are bright hyperechoic structures. Spontaneous echo contrast can only add as a surrogate marker to the stasis of blood. Thus, pre-op diagnosis needs an extremely high index of suspicion of GPA.

The CHB in this patient can be explained both by the GPA inflammatory process as well as by the RHD and a clear-cut distinction as to the cause of CHB in our case can only be presumptive.

Considering the rarity of GPA cardiac afflictions, it is highly unlikely a preoperative diagnosis of GPA will be made with certainty in most clinical scenarios. Even if suspected preoperatively and worked up, seronegativity (absence of C and P ANCA titres) can make the preoperative identification of GPA difficult.

Conclusion

Pre-operatively, GPA should be suspected if one encounters ocular, pulmonary, or renal manifestations along with raised ESR and serological markers (C and P ANCA). Intra-operatively, if the surgeon only sees a mitral valve orifice with no delineation of valvular tissue or myocardial tissue, as well as the presence of a thick whitish fibro elastic membrane lining the LA wall, mitral valve, and myocardium, GPA should be strongly suspected. All excised tissue must be sent for biopsy and the pathologist warned about the diagnosis. A correct diagnosis ensures the prompt initiation of appropriate medical treatment like steroids and other immunomodulators.

Funding

None.

Declarations

Ethics committee approval

As no patient identifiable data or picture is included in the case report, ethical committee approval was not obtained.

Informed consent to publish

Obtained.

Conflict of interest

The authors declare no competing interests.