Right ventricular mobile thrombus in end-stage hypertrophic cardiomyopathy

Abstract

We report the first case of a mobile right ventricular apical thrombus in hypertrophic cardiomyopathy in the absence of right ventricular apical aneurysm.

An 87-year-old man who had been diagnosed as having hypertrophic cardiomyopathy presented with gross peripheral edema and exertional dyspnea. He had been on warfarin, β-blockade, and diuretics. Electrocardiograms indicated progression of the disease with atrial fibrillation, low voltage and prominent Q waves in the left precordial leads. Echocardiograms revealed ventricular septal and apical hypertrophy, hypokinetic distal left ventricle, and dilated and severely hypokinetic right ventricle. A mobile thrombus (18 mm × 18 mm) was detected in the right ventricular apex. Cardiac computed tomography and magnetic resonance imaging confirmed a large thrombus in the right ventricular apex. Late gadolinium enhancement was present in the interventricular septum and distal segments of both ventricles, indicating myocardial fibrosis and scar.

A dilated and poorly contracting right ventricle, particularly right ventricular apex, in end-stage hypertrophic cardiomyopathy, associated with stagnant blood flow in the apex, was hypothesized as being responsible for right ventricular apical thrombus formation in the absence of right ventricular aneurysm.

<Learning objective: This is the first report of a mobile thrombus in the right ventricle in hypertrophic cardiomyopathy. Since mobile right ventricular thrombi may cause life-threatening pulmonary embolism, and detection of thrombi in the right ventricular apex may be difficult by echocardiographic examination, we suggest the use of cardiac computed tomography and/or magnetic resonance imaging that are useful tools to detect right ventricular apical thrombi when severe right ventricular dysfunction is suspected in end-stage hypertrophic cardiomyopathy.>

Introduction

Right ventricular (RV) thrombi may develop as a result of blood stagnation in patients with dilated cardiomyopathy [1], [2], [3] and arrhythmogenic RV cardiomyopathy [4], or in those with myocardial infarction that involves RV wall [5]. They have not been reported in patients with hypertrophic cardiomyopathy (HCM), although left ventricular (LV) apical thrombus is a relatively well-recognized complication of HCM with LV apical aneurysm. Immobile RV thrombi that develop in situ have a generally good prognosis when treated with anticoagulation therapy. On the other hand, mobile or floating RV thrombi are associated with a high mortality because they can embolize at any time [1], [2], [3], [4], [5]. We report a mobile RV thrombus that has not been previously described in patients with HCM.

Case report

An 87-year-old man presented with gross peripheral edema and exertional dyspnea. He had been diagnosed as having HCM of Maron type III and had been on warfarin for the previous four years as well as β-blockade and diuretics for two years because of several previous episodes of paroxysmal atrial fibrillation and heart failure. Electrocardiograms indicated progression of the disease with development of atrial fibrillation, low voltage and prominent Q waves in the left precordial leads (Fig. 1). Serum level of troponin T (0.112 ng/ml) and plasma level of B-type natriuretic peptide (1852 pg/ml) were both elevated. Prothrombin time/international normalized ratio (INR) was within normal therapeutic range (2.0–2.4) for his age. An echocardiogram revealed moderately and diffusely thickened ventricular septum (15 mm) with asymmetric septal and apical hypertrophy and non-dilated left ventricle (Diastolic dimension 48 mm, Systolic dimension 29 mm). However, also detected were severely hypokinetic distal left ventricle with poor distensibility and dilated and severely hypokinetic right ventricle which gradually developed since the first diagnosis 18 years previously (Fig. 2A). A mobile thrombus (18 mm × 18 mm) was detected in the RV apex (Fig. 2B). A contrast echocardiogram failed to show any echo-contrast in the RV apex, indicating stagnant blood flow in the RV apex. Since echocardiography is sometimes inadequate to distinguish between intracardiac thrombi and cardiac tumors because of its limited tissue characterization, enhanced multislice computed tomography (CT) was performed. It confirmed a large thrombus in the RV apex. Cardiac magnetic resonance imaging (MRI) also excluded cardiac tumors and confirmed an RV apical thrombus. Thinning of the wall was also present in the distal segments of both ventricles (Fig. 3A). Late gadolinium enhancement was detected in the interventricular septum and distal segments of both ventricles, indicating myocardial fibrosis and scar (Fig. 3B).

Fig. 1.

(A) Electrocardiogram in 2003 shows normal sinus rhythm with significant left ventricular hypertrophy. (B) Electrocardiogram in 2013 shows development of atrial fibrillation, low voltage in limb leads, and prominent Q waves in left precordial leads, indicating progression of the disease.

Fig. 2.

(A) Two-dimensional echocardiogram in the long-axis view shows moderately thickened ventricular septum, reduced wall motion of the distal left ventricle, and hypokinetic right ventricle. (B) A mobile thrombus (arrow) was detected in the right ventricular apex.

IVS, interventricular septum; LA, left atrium; LV, left ventricle; RV, right ventricle.

Fig. 3.

(A) Cardiac magnetic resonance imaging shows a right ventricular apical thrombus (arrow). (B) Late gadolinium enhancement was present in the interventricular septum and apical segments (arrows), indicating myocardial fibrosis and scar.

IVS, interventricular septum; LV, left ventricle; RA, right atrium; RV, right ventricle.

Although intensive anticoagulation with warfarin controlling INR at a range of 2.8–3.0 made the RV apical thrombus smaller (10 mm × 17 mm), it was not successful to resolve thrombi completely. Despite attempts to control heart failure, the patient died of refractory heart failure 40 days after admission.

Discussion

To the best of our knowledge, this is the first report of a RV mobile thrombus in HCM. RV apical aneurysm was not present in our patient. RV thrombi may develop in patients with dilated cardiomyopathy, arrhythmogenic RV cardiomyopathy, myocarditis, and myocardial infarction involving the right ventricle or in those with a foreign body such as pacemaker leads, as a result of stagnant blood flow because of dilated and poorly contracting right ventricle [1], [2], [3], [4], [5]. Based on long-term and gradual evolution of LV morphology in this patient, it is postulated that significant myopathic processes similar to LV pathology may be present in the RV and may be responsible for the formation of a RV thrombus in this particular patient with end-stage HCM. Since mobile or floating RV thrombi may cause life-threatening pulmonary embolism [1], [2], [3], [4], [5], and detection of thrombi in the RV apex may at times be difficult by echocardiographic examination, it is suggested that RV apical thrombi should be carefully sought by cardiac CT and/or cardiac MRI, particularly in those with end-stage HCM. Cardiac CT and cardiac MRI are also helpful in differentiating intracardiac thrombi from cardiac tumors.

The evolution in cardiac morphology, which is called LV remodeling with changes in wall thickness and cavity size, occurs in patients with HCM. This includes rapid and marked LV wall thickening often seen during adolescence and progressive LV wall thinning and cavity dilatation usually during midlife and late life [6], [7]. The latter evolution in the natural history of HCM may occur in a relatively small subset of patients and usually results in refractory heart failure, as shown in our patient. This is often designated as “end-stage” phase. At this stage, standard drug therapy such as β-blockade is redirected to usual heart failure treatment [8].

As far as a mechanism of RV thrombus formation is concerned, a dilated and poorly contracting RV, particularly RV apex, in end-stage HCM associated with blood stagnation in the RV apex is hypothesized as being responsible for the mobile RV apical thrombus formation in the absence of RV apical aneurysm. However, it is difficult to understand why a RV thrombus has developed in a patient on warfarin with adequate therapeutic INR range. The pathophysiologic mechanisms for RV thrombus formation are probably dependent on the so-called “Virchow’s triad”, i.e. stasis of blood, endotherial dysfunction, and a hypercoagulable state. A thrombus formation may occur in patients with fluctuating INRs, the clotting disorder such as lupus anticoagulant or antiphospholipid antibody syndrome, and cancer, in spite of a patient being on warfarin [9]. This is called “warfarin failure”. Our patient did not have any of these situations. However, warfarin failure occurs in some patients despite adequate warfarin anticoagulation. It is possible that thrombus cannot be resolved despite anticoagulation therapy when the severity of Virchow’s triad is far more powerful against warfarin anticoagulation. It is well recognized that the coagulation system is activated in HCM. Thus, blood stagnation in the poorly contracting RV apex may provide the basis of thrombus formation that is resistant against anticoagulation. Another possibility is the hypercoagulability secondary to occult malignancy, so-called Trousseau’s syndrome [10]. Tumor cells and their products exert procoagulant effects by activating the coagulation cascade and also by inhibiting the fibrinolytic system. In any case, it is important to recognize that a ventricular thrombus at times cannot be resolved by strict anticoagulation in end-stage HCM with biventricular failure.

In conclusion, we report the first case of end-stage HCM complicated with a mobile RV apical thrombus in the absence of RV apical aneurysm. In addition to echocardiography, we suggest the use of cardiac CT and/or cardiac MRI that are useful tools to detect RV apical thrombi and also to exclude intracardiac tumors when severe RV dysfunction is suspected in end-stage HCM, in order further to avoid life-threatening pulmonary embolism.

Conflict of interest

All authors have no conflict of interest.