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Keywords:

  • Cardiac transplant;
  • thrombus;
  • thrombotic complications;
  • tumor

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Discussion
  5. Acknowledgements
  6. Disclosure
  7. References

Atrial masses postcardiac transplant are not well reported and their diagnosis and treatment can be challenging. In the asymptomatic patient, differentiating thrombus from cardiac tumor can sometimes be difficult and the use of multiple imaging modalities is recommended. Accurate diagnosis is imperative to inform a treatment plan that balances the benefits and risks of a medical versus surgical approach. We present three cases of atrial masses postcardiac transplant to illustrate this clinical dilemma.


Abbreviations: 
AF

atrial fibrillation

CAV

coronary artery vasculopathy

CMR

cardiac magnetic resonance imaging

DSE

dobutamine stress echocardiogram

IAS

inter-atrial septum

ICE

intracardiac echocardiography

IDCM

idiopathic dilated cardiomyopathy

LA

left atrial

LAA

left atrial appendage

LV

left ventricular

LVAD

left ventricular assist device

PM

pacemaker

RA

right atrial

SEC

spontaneous echo contrast

TEE

trans-esophageal echocardiogram

TTE

trans-thoracic echocardiogram

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Discussion
  5. Acknowledgements
  6. Disclosure
  7. References

The precise incidence of cardiac masses postorthotopic heart transplantation is not clear as the literature is limited to isolated case reports. Atrial masses occur more commonly than ventricular masses where diagnostic efforts are aimed at differentiating cardiac thrombus, tumors, infective lesions and anatomical variants. Cardiac transplant patients are at an increased risk for these complications as chronic immunosuppression increases the risk of both infection and malignancy, and various factors often predispose them to thrombus formation. However, the correct diagnosis can sometimes be difficult with certainty only being achieved when a pathological specimen is obtained. We present three cases of atrial masses postcardiac transplant to illustrate this clinical dilemma.

Case 1

A man with an idiopathic dilated cardiomyopathy (IDCM) who received a heart transplant (bicaval anastamotic technique) at age 44 in 1998. The donor was a 25-year old male in a motor vehicle accident with normal cardiac function. The recipient required creation of a surgical pericardial window in the first 6 months posttransplant for recurrent pericardial effusions but otherwise progressed well. In 2007, 9 years posttransplant, a routine Dobutamine Stress Echocardiogram (DSE) noted an incidental 23 × 13 mm left atrial (LA) mass that was attached to the inter-atrial septum (IAS), with minimal mobility. A trans-esophageal echocardiogram (TEE) showed the mass had a broad based attachment to both the distal IAS and base of the anterior mitral valve leaflet, and may have been contributing to mild to moderate mitral regurgitation (Figure 1A). A retrospective review of previous trans-thoracic echocardiograms (TTE) showed that the mass was likely visible in some views 2 years earlier. A cardiac magnetic resonance imaging scan (CMR) found the signal characteristics, and enhancement with contrast to be highly suggestive of an atrial myxoma, though the location atypical. The patient underwent surgery that confirmed the mass attachment extended from the roof of the LA to the mid-portion of the anterior leaflet of the mitral valve, and its removal necessitated insertion of a bioprosthetic mitral valve (Figure 1B). The patient recovered well and pathological examination revealed a myxoma with extensive neovascularization. Currently, the patient is well and shows no evidence of myxoma recurrence.

image

Figure 1. (A) TEE showing mass attached to base of the anterior leaflet of the mitral valve and (B) mass postresection showing attachment to IAS.

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Case 2

A girl with Hypertrophic Cardiomyopathy and obesity who received a heart transplant (bi-atrial anastamotic technique with patent foramen ovale closure at time of transplant) at age 13 in April 2005. Pretransplant, she developed progressive cardiac and renal failure requiring bridging to transplantation for 3 days with a Berlin Heart Left Ventricular Assist Device (LVAD). The donor was a 31 years old with an intracranial bleed that was of a similar weight match. She had a complicated postoperative course including hemorrhagic stroke (recovered well), sternal wound infections requiring multiple debridements and an episode of Grade 4 severe rejection in October 2005 due to medication noncompliance. She had very poor acoustic windows but TTEs from 2006 onwards suggested a mobile right atrial (RA) mass attached to the IAS measuring approximately 22 × 19 mm. This was thought to represent a thrombus but the risks of anticoagulating a patient with previous hemorrhagic stroke and compliance issues was thought to outweigh the benefit, therefore the lesion was followed with echocardiography. In 2008, management was transferred to an adult cardiac center where a repeat TTE showed a similar sized lesion. Late 2008 a CMR was performed which showed a nonenhancing mass attached to the IAS via a small pedicle or stalk, again thought to likely represent a thrombus (Figure 2). At this stage anti-coagulation was deemed safe and Warfarin was commenced with a plan to repeat the CMR in 3–6 months. In September 2009, the repeat CMR showed no significant change with Warfarin, and the possibility of a nonenhancing pure myxomatous myxoma was considered. Surgical and conservative treatment plans were both considered at this stage but the patient preferred a definitive surgical approach. Under direct vision during surgical removal it was still not clear whether the mass represented a myxoma or calcified thrombus. Pathological examination revealed a calcified old thrombus with a fibrous stalk. The patient recovered well and there was no evidence of recurrence of the lesion on a repeat CMR in 2010 (now off anticoagulation).

image

Figure 2. CMR in late 2008 showing a right atrial mass attached to the IAS.

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Case 3

A woman with IDCM who received a heart transplant at age 45 in 1992. In 2008, 16 years posttransplant, she was diagnosed with noninvasive moderately differentiated anal squamous cell cancer which was treated with chemo- and radiotherapy with good response. Other posttransplant complications included chronic renal failure (creatinine 150–160 μmol/L), mild coronary artery vasculopathy (CAV), cigarette smoking and postmenopausal symptoms treated with hormone replacement therapy. There was no posttransplant history of atrial fibrillation or flutter. In 2011 a routine DSE showed a new LA mass measuring 35 × 18 mm (Figure 3A). The same day the patient had a technically sub-optimal noncontrast CMR which showed the mass to arise from the superior aspect of the LA (Figure 3B). A noncontrast computed tomography (CT) chest scan excluded extra-cardiac extension or any pulmonary lesions. The mass was thought to be either thrombus or a tumor (metastatic) and anticoagulation was commenced. One month later a TEE showed a similar-sized lesion with a broad based attachment. Due to concerns about metastatic disease and potential embolic events, plans were made to excise the lesion if a repeat TTE did not show resolution. However, a TTE, 2 months after commencing Warfarin, showed the lesion was smaller and a TTE at 3.5 months showed no evidence of a mass. The lesion was therefore thought to have been a thrombus. The patient is now over 19 years posttransplant and remains well on anticoagulation.

image

Figure 3. (A) TTE showing LA mass and (B) CMR showing mass in superior aspect of LA.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Discussion
  5. Acknowledgements
  6. Disclosure
  7. References

Most atrial masses postcardiac transplant are discovered on routine TTE or DSE. Infective endocarditis should always be considered in the differential diagnosis, though this is more likely when the patient's clinical status is consistent with an infective process. In the asymptomatic patient, thrombus or tumor is more probable, but can be difficult to distinguish.

Virchow's triad still holds true postcardiac transplantation, and any factors that cause a hypercoagulable state, disruption to flow, or endothelial or vessel wall injury can promote thrombus formation. Patients with atrial fibrillation, large LA, low cardiac output states (possibly due to rejection or CAV) and absence of anticoagulation are at increased risk of thrombus formation. Thrombus should be suspected when masses form in close proximity to suture lines or foreign objects (e.g. pacing wires or catheters), and when they develop in a relatively short time period. Operative technique is also important as patients who undergo the preferred ‘bicaval’ anastamotic technique rather than the more traditional ‘bi-atrial’ approach tend to have smaller LA size with less spontaneous echo contrast (SEC), thrombus and embolic events (1–3).

In nontransplant patients, cardiac tumors are more likely to be secondary than primary with autopsy studies reporting a frequency of 8.4% (in patients with known cancer) and up to 0.03%, respectively (4,5). Most primary tumors are benign myxomas or papillary fibroelastomas, while malignant primaries are predominantly sarcomas, with occasional lymphomas and mesotheliomas (Table 1). Although malignancy postcardiac transplantation occurs more commonly than the general population, the reporting of primary cardiac malignancies is limited to individual case reports. Apart from our Case 1, there are two other documented cases of pathologically proven myxoma postcardiac transplant (11,12). In both cases, the myxoma was attached via a pedicle arising from a left atrial suture line rather than the classical location on the IAS, highlighting potential diagnostic pitfalls. When a primary cardiac tumor is suspected, definitive treatment is often sought since approximately 25% present with embolic events (more likely with small tumors involving the aortic valve or left atrium) (13).

Table 1.  General features and imaging characteristics of common atrial masses6–10
 General ConsiderationsThrombusMyxomaPapillary fibroelastomaSarcoma
  1. TTE = trans-thoracic echocardiography; TEE = trans-esophageal echocardiography; CT = computed tomography; MRI = magnetic resonance imaging; AF = atrial fibrillation; LV = left ventricular; LA = left atrium; IAS = inter-atrial septum; RA = right atrium, PM = pacemaker; SEC = spontaneous echo contrast; LAA = left atrial appendage.

General featuresThrombi > tumors Secondary > primary tumors 75–94% primary tumors are benignHomogenous appearance Suture/foreign body sites Rapid onset Coagulopathic AF, LV dysfunction, large LA50–80% of benign tumors 75% in LA Attached to fossa ovalis (IAS) Attached via stalk/pedicle Typically ovoid/spherical Heterogenous appearance10–25% of benign tumors Small (<1 cm) usually solitary Affects left sided heart valves “Flower-like” with fronds95% of primary malignancies Most common in RA Broad based Locally invasive/metastases Poor prognosis
ECHO (TTE/TEE)Cost-effective Easily available Hemodynamic assessment Contrast/3D add informationBest for PM lead assessment TEE assesses SEC, LAA, IAS well No contrast uptake No color flow within massPedicle often best seen on TEE Assesses tumor mobility well Hemodynamic effectsModality of choice “Shimmering” appearance Valvular function sparedHemodynamic effects Pericardial effusion
CTBest for thoracic extension Coronary artery assessment Radiation Contrast nephrotoxicityLow attenuation mass Possible calcific foci if chronic No contrast uptakeLow attenuation Heterogenous contrast uptakeOften difficult to visualizeHeterogenous contrast uptake Tumor extension/spread
MRIBest tissue characterization No radiation/contrast safer Cardiac device incompatible Availability/cost possible issueT1/T2 dependent on clot age No contrast uptakeIsointense in T1 Hyperintense in T2 Heterogenous contrast uptakeOften difficult to visualizeHeterogenous in T1 Hyperintense in T2 “Cauliflower” appearance Enhances with contrast

TTE is a noninvasive, readily available and cost-effective imaging modality that can inform on mass morphology, location and hemodynamic consequences. TEE is a useful adjunct to provide additional resolution and information about SEC, the left atrial appendage and the IAS. However, for cardiac transplant patients, relying solely on echocardiography to differentiate intra-cardiac masses can result in misdiagnoses (14,15). Cardiac MRI (with contrast) adds significant diagnostic accuracy for intra-cardiac masses, and is highly recommended as a complementary imaging modality when available (9,16). CT can also be helpful when MRI is contra-indicated, especially for coronary artery assessment and extra-cardiac thoracic evaluation (8,9; Table 1).

When malignancy is suspected, transvenous cardiac biopsy can be utilized to obtain pathology, especially when complete surgical resection is thought not possible or too risky. Biopsy guidance with TTE, TEE or intracardiac echocardiography (ICE) improves diagnostic sampling and safety, and right sided masses are preferred due to a lower risk of systemic embolization (17–19).

Treatment plans for atrial masses postcardiac transplant should be individualized given the lack of clinical trial information. Most benign atrial tumors will need consideration for surgical removal to avoid complications of mass effect or embolization (6,20). Most posttransplant atrial thrombi can safely undergo a trial of anticoagulation, although there is little evidence to support the best approach in large ‘ball-like’ thrombi, or when anticoagulation fails to have effect (21,22). When diagnostic uncertainty exists, a trial of anticoagulation of at least 4 weeks with repeat imaging to examine for a response seems prudent (23) The chosen treatment course should balance the risk of conservative treatment/anticoagulation with the operative risk of surgical intervention, whilst considering patient preferences.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Discussion
  5. Acknowledgements
  6. Disclosure
  7. References

The authors wish to thank Dr. Victor Lawrence Wycoco (MBBS Hons, FRANZCR) for his assistance in preparation of the presented images. No specific funding was provided for this study.

Disclosure

  1. Top of page
  2. Abstract
  3. Introduction
  4. Discussion
  5. Acknowledgements
  6. Disclosure
  7. References

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Discussion
  5. Acknowledgements
  6. Disclosure
  7. References