Successful thrombolysis of mechanical mitral valve prosthesis in a patient with cardiogenic shock

Abstract

A 48-year-old woman with cardiogenic shock was admitted to a nearby hospital. Her medical history included mechanical replacement of her mitral valve 4 years previously in Russia because of rheumatic stenosis. On admission, her international normalised ratio (INR) was significantly reduced below the therapeutic limit. A severe stenosis of the valve prosthesis was identified by transthoracic and transoesophageal echocardiography and the patient was transferred to our university hospital for discussion of an immediate therapeutic procedure and to ensure cardiac surgical backup. Here, the patient’s poor clinical status led to the decision for a non-routine treatment: a successful series of intravenous thrombolysis with alteplase. Clinical symptoms and echocardiographic parameters improved significantly.

BACKGROUND

Higher life expectancy has lead to increasing indications for native heart valve replacement by mechanical prostheses or tissue bioprostheses. The most threatening complication is valve thrombosis, caused by local formation of a thrombus or pannus. The overall incidence of mechanical prosthetic valve obstruction is 0.1% to 4.0% per patient year, depending on the type and site of the prosthesis, being higher in mitral than aortic position.¹ Inadequate anticoagulant therapy is the most predisposing factor for prosthetic heart valve thrombosis.^2–4 Surgical intervention is the conventional treatment of choice but has a high mortality rate especially in patients with heart failure (New York Heart Association (NYHA) class III and IV) who often show serious comorbidities.² This has stimulated the development of alternative therapeutic approaches such as thrombolysis. Thrombolytic therapy already represents the first choice treatment for thrombotic tricuspid or pulmonary prostheses because success rates are high with a low risk of cerebrovascular accidents.^3,5 However, thrombolysis remains a controversial treatment for aortic and mitral mechanical valve thrombosis due to the risks of thromboembolic and haemorrhagic events of left-sided valves.⁶

The present case study describes a patient with acute thrombosis of her mechanical mitral valve prosthesis. She presented with cardiogenic shock. Because of her poor clinical condition we had to make a decision on therapeutic procedure immediately. We performed an acute intravenous thrombolysis, which showed excellent results. We decided to publish this case because this therapeutic option is not a routine procedure according to international guidelines. However, in view of the growing number of patients with valve prostheses who are older and multimorbid, it may play an increasing role in the future.

CASE PRESENTATION

A 48-year-old woman was admitted to a nearby small hospital with cardiogenic shock, orthopnoea, bilateral pleural effusions and anuria. The symptoms had started approximately 5 days before and had rapidly worsened despite an increased dose of diuretic medication, initiated by her doctor. Transoesophageal echocardiography and x ray fluoroscopy lead to the diagnosis of a severe stenosis of her mechanical mitral valve prosthesis. The patient was transferred to our university hospital for interdisciplinary discussion of cardiologists and cardiac surgeons on the therapeutic procedure and to ensure surgical standby.

Her past medical history included rheumatic mitral valve stenosis with mechanical valve replacement (tilting disc “MIKS 27 mm”) and De Vega plastic of her tricuspidal valve in Russia 4 years before.

On admission, her physical examination revealed tachypnoe (29 breaths per min) with ventilatory effort, atrial fibrillation with rapid ventricular response (138 beats per min) and arterial hypotension (90/60 mm Hg). She was oriented to person, place, time and situation and had no neurological deficits. Vesicular breath sounds at lung bases were severely decreased, moist rales were present in the lower two-thirds bilaterally. She presented a mild mid-diastolic murmur with a maximum over the fourth to fifth intercostalic room and massive oedema on the lower extremity.

Taken together, the patient presented with cardiogenic shock, the beginnings of lung oedema and signs of global heart failure.

INVESTIGATIONS

The electrocardiogram confirmed atrial fibrillation without signs of acute myocardial ischaemia. After the application of short-acting β-blockers to decrease the heart rate and prolong diastolic time, she converted into sinus rhythm. Chest radiography revealed an acute cardiac congestion and interstitial pulmonary oedema (fig 1). Blood analysis revealed a haemoglobin level of 11.6 g/dl and lactate dehydrogenase of 367 U/litre. Due to malcompliance, the international normalised ratio (INR) was low (1.1), the target range in mechanical valve prosthesis being 2.5–3.5.

Figure 1.

Chest x ray performed at admission showing an acute cardiac congestion and interstitial pulmonary oedema. x Ray fluoroscopy showing a reduced opening of the tilting disc (arrow). Transoesophageal echocardiography demonstrated a severe stenosis of the mechanical mitral valve with an opening area calculated at 0.9 cm².

On admission, transthoracic and transoesophageal echocardiograms were performed immediately. They showed a normal left ventricular systolic function and significantly enlarged left atrium (54 mm). The pulmonary artery systolic pressure was estimated at 69 mm Hg. A severe stenosis of the mechanical mitral valve prosthesis with an opening calculated at 0.9 cm² (pressure half-time (PHT) and continuity equation) was documented (fig 1). A turbulent flow and high transprosthetic mean diastolic gradient of 28.2 mm Hg and maximal gradient of 47.9 mm Hg were estimated. A hyperechoic structure adherent at the level of the valve ring reaching towards the left atrium and ventricle was documented. The appearance of this mass was compatible with a recently formed thrombus. In addition, x ray fluoroscopy showed a reduced opening of the tilting disc prosthesis.

DIFFERENTIAL DIAGNOSIS

The malfunction of her mechanical mitral valve prosthesis may have been also due to a structural problem of the valve itself. Damages such as leaflet immobility or inappropriate size of implant have been described previously.^7,8 Furthermore, valve-obstructing material can also be correlated to valve endocarditis.

TREATMENT

Altogether, acute thrombosis of the mechanical mitral valve prosthesis was identified as the cause of the patient’s cardiogenic shock. The patient’s cardiac and respiratory function rapidly deteriorated. Due to her poor clinical condition, the decision for acute thrombolytic treatment, versus immediate valve surgery, was made in agreement with our cardiac surgeons. The patient’s informed consent was obtained. According to guidelines and standard dosage protocols, a bolus of 10 mg alteplase (Boehringer Ingelheim, Ingelheim, Germany) was followed by 90 mg in continuous intravenous infusion for 1.5 h.² Thereafter, anticoagulation with unfractionated heparin and strict monitoring of partial thromboplastin time (PTT) values (target 55–80 s) were performed.

Immediately at the end of the thrombolytic infusion, the patient’s clinical status improved significantly. After two series of intravenous thrombolysis, the transthoracic echocardiogram showed a decrease in the mean pressure gradient across the mitral valve prosthesis from 28.2 mm Hg to 6.8 mm Hg, maximal pressure from 47.9 mm Hg to 13.2 mm Hg respectively (fig 2). Significant opening moves of the valve and opening area of 1.9 cm² (PHT and continuity equation) were documented. Some days later, echocardiographic findings indicated a nearly normalised function of the prosthetic valve, suggesting complete dissolution of the thrombus.

Figure 2.

x Ray fluoroscopy performed after thrombolytic therapy shows better opening movement of the valve (arrow).

OUTCOME AND FOLLOW-UP

After 26 days (the patient was observed for suspected lung tuberculosis in the meantime), the patient was discharged in good clinical condition. We recommended the maintenance of INR values between 2.5 and 3.5 and was given concomitant medication of 100 mg aspirin per day according to class I indication in the 2006 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for patients with mechanical valves.⁹ For the next 6 months, a strict follow-up with monthly echocardiography was scheduled. At her first follow-up 1 month later, the patient presented clinically well. Echocardiography showed a good function of her mitral valve prosthesis. However, the INR value (1.3) was below the therapeutic range again, possibly due to the patient’s continuing malcompliance.

DISCUSSION

Obstructive valve thrombosis should be suspected in patients with prosthetic valve replacement and sudden increase in shortness of breath or symptoms of thromboembolism. In our case, the patient presented with a short history of rapidly progressive dyspnoea and finally cardiogenic shock.

To determine the existence and location of a thrombotic mass in prosthetic valve obstruction, transthoracic or ideally transoesophageal echocardiography are by far the most accurate diagnostic tools.¹⁰ The transthoracic echocardiogram identifies a substantial increase in the transvalvular pressure gradient by Doppler examination. A thrombotic mass or malfunction of the prosthetic leaflets may also be documented. x Ray fluoroscopy detects alterations in the movement of prosthetic leaflets and variations in the opening and closure angles.¹¹ Thus, the most appropriate treatment can be chosen.

Mechanical valve prosthesis obstruction is a severe complication and may be caused by a local thrombus formation, fibrous tissue (pannus) ingrowth or the combination of both. Thrombosis appears to be the major cause of valve occlusion, observed in operative findings.¹² The differential diagnosis of thrombotic mechanical valve obstruction versus pannus formation has important implications since selected patients with thrombus, not pannus, may benefit from thrombolytic therapy instead of repeat surgery.¹³ To distinguish between thrombotic mechanical valve obstruction and pannus formation, clinical and echocardiographic criteria have been formulated. In patients that have undergone valve surgery for mechanical valve prosthesis obstruction, the findings of pure thrombi were likely in patients with ineffective anticoagulation and rapid onset of symptoms (<1 month).¹⁴ In the echocardiogram, thrombi appear as larger soft masses whereas panni are smaller and show a higher echodensity. Besides, thrombi on mitral valve prostheses, rather than pannus formations, tend to expand more often towards the left atrium.

In general, obstruction of native or mechanical mitral valves can also be caused by thrombi dislodged from the left atrial appendage.^15,16 As in our case, patients with an enlarged left atrium tend to have a high likelihood for atrial fibrillation and consequently for the development of left atrial appendage thrombi, which can prolapse into the mitral valve area. However, our patient’s transoesophageal echocardiography ruled out any thrombotic material attached to the left atrium.

To compare the outcome of surgery with thrombolysis in prosthetic heart valve thrombosis, no randomised trials exist because of the small number of cases and diverse factors influencing the therapeutic decision. However, in the 1990s some case reports have shown an overall good outcome of mechanical mitral valve thrombolysis.^17–19 European Society of Cardiology (ESC) guidelines²⁰ recommend valve replacement in obstructive thrombosis as the treatment of choice in patients who are critically ill without serious comorbidity (recommendation class I, level of evidence C). Fibrinolysis should be considered in patients who are critically ill and unlikely to survive operation because of comorbidities, in institutions where cardiac surgery is not available or in thrombotic tricuspidal or pulmonary prostheses. In patients with class I and II NYHA heart failure, low mortality of surgery versus the high risk of 12% to 17% of embolism due to thrombolysis.^5,21 In the presence of a pannus, chronic thrombosis of mitral protheses, fibrinolysis is less likely to be successful.

To evaluate the success rate of thrombolytic therapy, a review of 200 reported cases of left-sided mechanical valve thrombosis was performed recently.⁵ The overall success rate was estimated to be 82%. Complications of thrombolysis included peripheral or cerebral embolism (12%), recurrent thrombosis of the valve (11%) and major (5%) and minor haemorrhages.⁵ Independent predictors of complications followed by thrombolysis are history of stroke and size of the thrombotic mass. For each 1cm² increase in the thrombus area, a 2.4-fold increase in complication rate results.²² Absolute contraindications to thrombolytic therapy include active internal haemorrhage, history of haemorrhagic stroke, brain tumour, massive arterial hypertension and recent surgical interventions.

In conclusion, our patient showed the typical clinical symptoms of dyspnoea, cardiac decompensation and even cardiogenic shock. This typically occurs in acutely obstructed mechanical mitral valve prosthesis along with characteristic echocardiographic criteria that are compatible with thrombus formation. Inadequate anticoagulation was also present in our patient. She was haemodynamically severe compromised, and had a particularly high surgical risk. Therefore, our report confirms the ESC guidelines that thrombolysis can be effective for the treatment of prosthetic valve thrombosis of left chambers in patients who are critically ill. It is a promising alternative treatment in mechanical valve thrombosis.

LEARNING POINTS

• Acute prosthetic mitral valve thrombosis is a life-threatening condition that requires immediate detection. It is characterised by an acute onset (<1 month) of symptoms (eg, shortness of breath, symptoms of thromboembolism). Inadequate anticoagulation is one of the main causes.

• Transthoracic/transoesophageal echocardiography and x ray fluoroscopy are appropriate tools in the diagnosis of prosthetic valve thrombosis and differentiation between a local thrombus (acute) and pannus formation (chronic ingrowth) as the cause of obstruction.

• Surgical intervention is the conventional treatment of choice in thrombosis of mechanical aortic and mitral valves, but can result in a high mortality. Acute thrombolytic therapy is a promising alternative to avoid surgical valve replacement also in left-sided valves and especially in patients who are critically ill. Patients with thrombus but not with pannus formation at the mechanical valve may benefit from thrombolytic therapy. It can result in immediate haemodynamic improvement and resolution of cardiogenic shock.