Right atrial mural thrombi: An autopsy study of an under-diagnosed complication at an unusual site.

BACKGROUND: Right atrial mural thrombi (RAMT) are often seen in association with cardiac diseases or foreign bodies. Unusual locations at the flutter isthmus and the atrial appendage prompted us to evaluate our 2-year autopsy data on such thrombi.
MATERIALS AND METHODS: In the 2-year retrospective autopsy, the clinical and autopsy records of patients with RAMT were reviewed, with particular reference to the presence of central venous catheter (CVC), its site of insertion, its type, material and size, its duration of placement, and the drugs infused through the catheter.
RESULTS: Of the 940 autopsies performed in 2 years, RAMT was seen in 24 hearts and was related to an insertion of a CVC in 23 patients (95.8%). The risk and/or associated factors for this complication were tunneled and polyethylene catheters, Intensive Care Unit admission, infused drugs, underlying cardiac diseases, and pregnancy. A noteworthy feature was the location of the thrombi in the flutter isthmus in 16 hearts (66.7%) and atrial appendage in another six hearts. Localized endocarditis/myocarditis and pulmonary thromboembolism were observed in six and four patients, respectively.
CONCLUSIONS: This autopsy study, which has a high incidence of catheter-related RAMT, does not reflect the true incidence but reiterates the importance of guided insertion of central venous and prompt recognition of thrombus formation.

Introduction

From the anatomic point of view, the atria are said to possess a body, a venous component, a vestibule, and an appendage. In the right atrium (RA), the body is virtually nonexistent. When one considers the pathophysiology and location of the right atrial mural thrombi (RAMT), two types have been described: Type A thrombi that are unattached, freely mobile lying in the vestibule (commonly referred to as “emboli-in-transit”) and Type B thrombi, which are attached to the right atrial free walls or to the cavoatrial junctions (toward the venous component).[1] These mural thrombi are seen more in association with cardiac diseases or foreign bodies. In the recent past at autopsy, we have noted the presence of thrombi attached to the flutter isthmus (a part of the right atrial vestibule below the coronary sinus and between the Eustachian valve and tricuspid annulus) and in the atrial appendage. These unusual locations prompted us to evaluate our 2-year autopsy data on RAMT.

Materials and Methods

A retrospective analysis of all autopsies performed by the Department of Pathology between January 2012 and December 2013 was performed for identifying RAMT. The clinical and autopsy records were reviewed. Patient demographics, duration of admission, modes of presentation, clinical diagnosis, and investigations were noted. If patients had a history of central venous catheterization, particular attention was paid to the site of central venous catheter (CVC) insertion, the type/material/size of CVC, duration of placement, and the drugs infused through the catheter. At autopsy, the site and size of the RAMT, pathology of the right atrial wall at the site of thrombosis and other associations/complications were noted along with other cardiac and extracardiac lesions.

Results

Of the 940 autopsies performed in 2 years, RAMT were seen in 24 hearts (2.55%). There were 19 females and 5 males with an age range of 2–70 years (mean age 30.9 years). The brief clinicopathological features have been given in Table 1. The patients had been admitted for a period ranging from 7 h to 27 days with a mean of 7 days. Eleven patients (48.8%) had been admitted to Intensive Care Units (ICUs) – eight in medical, two in surgical, and one in pediatric ICUs. Among the 19 women, 12 (63.2%) were pregnant. A history of insertion of CVC was present in 23 patients (95.8%). The duration of CVC insertion ranged from 2 to 36 days (mean 6.82 days). In the adult patients, the size of the catheter was 7 Fr, and the catheter size had not been selected as per the built of the patients. The catheters were made up of polyethylene. Cephalosporins were the most common drug (12 patients) infused through the catheter, followed by metronidazole, vancomycin, and meropenem. Underlying cardiac disease was present in six patients and remained undiagnosed in two patients (cases 12 and 15). A noteworthy feature was the location of the thrombi in the flutter isthmus in 16 hearts (66.7%) seen as flaky granularity, plaques, or large space-occupying masses; four among them also showed thrombi at other sites [Figure 1]. In addition, they were present in the atrial appendage in another six hearts. Localized endocarditis/myocarditis and pulmonary thromboembolism (PTE) [Figure 2] were observed in six and four patients, respectively.

Table 1

Right atrial mural thrombi – clinicopathological features (n=24)

Clinical diagnoses	7
Pregnancy-induced complications Infections	6
Rheumatic heart disease	3
Atherosclerotic vascular disease	2
Tumors	2
Acute pancreatitis	1
Burns	1
Toxic fume inhalation	1
Severe anemia	1
Sites of thrombus
Flutter isthmus	16
Superior cavoatrial junction	4
Right atrial appendage	7
Right ventricle	1
Left ventricle	1
Risk factors
Central venous catheter insertion	18
Intensive Care Unit admission	11
Pregnancy	12
Cardiac disease	4
Malignancy	1
Thrombus-related complications
Pulmonary thromboembolism	04
Endocarditis	6
Myocarditis	2

Figure 1

Thrombus (black arrows) is seen at the flutter isthmus as (a) fine endocardial granularity; (b) plaque of flaky friable yellowish-white material and (c) large reddish-brown mass. In the last panel, there is a cylindrical tract of thrombus (white arrow) in relation to the opening of superior vena cava. ATL: Anterior tricuspid leaflet, FO: Fossa ovalis, PTL: Posterior tricuspid leaflet, RA: Right atrium, RV: Right ventricle, STL: Septal tricuspid leaflet, TV: Tricuspid valve, SVC: Superior vena cava

Figure 2

(a) Thrombus T is adherent to an inflamed endocardium E. The underlying myocardium also shows the presence of inflammatory cells (H and E, ×400). (b) There is transmural inflammation of the right atrial wall at the site of the thrombus (H and E, ×400). (c) The right lung shows subpleural wedge-shaped hemorrhagic zones of infarction in the middle and lower lobes

Discussion

In this short 2-year study, we found that most of the RAMTs occurred in all probability to CVC insertion, and more than 50% of the thrombi were located at an unusual site, namely the flutter isthmus. CVC insertion is a common procedure performed particularly in ICUs to monitor central venous (CV) pressure and to guide fluid replacement therapy, especially in sepsis and septic shock.[2] The other uses include regular hematological or biochemical monitoring antimicrobial administration, giving hemodialysis and total parenteral nutrition. The access to the central veins is achieved in most cases through peripheral veins, namely the internal jugular or subclavian veins as was the case in all our patients. Despite the ease of insertion, the procedure is prone to problems and complications, which can be early or late. Early complications occur during the procedure or within 24 h are mechanical in nature and include inadvertent pneumothorax/hemothorax, catheter breakage, extravasation of infused fluids, nerve injury, or even cardiac tamponade.[2] Late complications develop after 24 h and include infections and thrombosis, which could be inter-related.[3]

Occurrences of thrombi in association with CVCs depend on several factors[4] and such thrombotic episodes occur to the extent of 2–67%, mostly in the veins of the upper extremities.[5] Important in the pathogenesis is an endothelial injury consequent to mechanical damage, catheter-related infections, or chemical injury produced by certain drugs and other infused fluids. Catheter characteristics in the form of size, material and type, side, sites and ease of insertion, duration of placement are additional important risk factors. Patient characteristics have also a role to play. Among the 24 patients, 50% were pregnant females. Pregnancy and the postpartum period are known prothrombotic states. Furthermore, 11 out of 24 patients (48.8%) were admitted to ICUs, and such critically ill patients are at a high risk of for deep vein thrombosis and thromboembolism.[6] The catheters used in our patients were nonsilicone and tunneled.

The incidence of catheter-related RAMT (CR-RAMT) is said to range from 12% to even 30% as reviewed by Burns and McLaren.[7] In this review[7] and in a review concerning hemodialysis catheters,[8] the thrombi were found attached to the tip of the catheter and if mural, the site of adherence had not be clearly delineated. In this study, CVCs were placed in 23 out of 24 patients (95.8%), and the thrombi were located solely at the superior cavoatrial junction (2 patients, 8.3%), in the right atrial appendage (6 patients, 25%), and over the flutter isthmus (16 patients, 66.7%). The appendage and the flutter isthmus are unusual sites, and we feel that this could be related to malposition of the tip. There have been recommendations that the catheter tip should be present at the distal portion of the superior vena cava or at its junction with RA as judged by a chest X-ray using the right tracheobronchial angle.[9] In these cases, it may be possible that there could have been coiling of the catheter at the flutter isthmus or at its entry into the right atrial appendage, probably related to a larger than appropriate CVC size or an over-insertion. In addition, migration rhythmic motions of the atrium or movements of the arm/patient could also be contributory. Endothelial injury by the guide-wire which is longer than the CVC is yet another possibility. Recognition of such thrombi is essential to prevent subsequent rare consequences. The thrombus can serve as a nidus for microbial colonization,[10] a feature seen in eight of our cases; septic foci elsewhere were already present in three patients. Another more ominous outcome was PTE which was seen in three of our patients. With CV insertion, PTE is reported to occur about 15% of patients with associated mortality in 28–30% of patients.[10] The fatality was seen in one (4.2%) of our patients.

CR-RAMTs are fortunately rare complications of CVCs but are unfortunately underdiagnosed and can also be potentially life-threatening. This autopsy study, which has a high incidence of CR-RAMT, does not reflect the true incidence but reiterates the importance of guided insertion of CV and prompt recognition of thrombus formation. Depending on the size of the thrombus, options of repeated screenings, anticoagulation therapy, thrombolysis, or thrombectomy are recommended to prevent further disastrous outcomes.[11]

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Conflicts of interest

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