This is a case of AL amyloid where the aggregating protein is an immunoglobulin light chain produced by a clonal population of plasma cells in the bone marrow. It can be associated with multiple myeloma. Half of all AL amyloid patients will have cardiac involvement of whom many develop heart failure.1
Low voltage (QRS voltage amplitude ≤0.5 mV in all the limb leads) is a common feature in cardiac amyloid. It reflects the fact that increasing myocardial thickness is due to an inert substance (amyloid) rather than viable myocardium. Typically, there is also a ‘pseudo-infarction’ pattern with Q-waves. Echocardiography provides a non-invasive assessment of cardiac involvement. Early deposition causes impaired cardiac relaxation, or ‘diastolic impairment’ with normal or only mildly reduced systolic function. Disease progression leads to thickened walls with poor compliance and restrictive physiology on echo Doppler studies. Characteristically, the ventricles retain normal dimensions but there is bi-atrial dilatation. With further protein accumulation, myocytes are lost, leading to additional systolic dysfunction. It is the combination of low voltage on the ECG and thick walls on echocardiography (a reduction in voltage:mass ratio) that provides the earliest clue that the heart is involved with amyloid deposition.
Atrial amyloid deposition can cause mechanical standstill with significant risks of atrial fibrillation and thrombus formation as occurred in our patient. Pulmonary involvement causes pulmonary hypertension and cor pulmonale leading to a very poor prognosis.
Alongside such cardiac investigations, serum and urine electrophoresis will aid the diagnosis with bone marrow biopsy required to identify the plasma cell clone.
The conduction system of the heart is also affected. Electrophysiological assessment in AL cardiomyopathy has shown abnormal prolongation of infra-His conduction times, predictive of death.2
This abnormality was present even when the QRS duration on the surface ECG was normal and this likely reflects extensive amyloid infiltration of the distal conduction system as well as fibrosis. Such subjects had a propensity for complete heart block and bradycardic death, often resulting in electromechanical dissociation.2
Other authors have described complete heart block and consequent asystole despite well placed pacing leads.3
Thus, while pacing improves symptoms, it does not appear to improve survival.4
The clinical value of biventricular pacemakers or implantable cardiac defibrillators is also questionable.5
Cardiac amyloid is a progressive disorder and is usually treated with conventional heart failure therapies with a focus on salt restriction and diuretics.6
Caution is required with digoxin because it binds avidly to the amyloid fibrils leading to toxicity. Ace inhibitors and angiotensin-receptor blockers have limited benefit in diastolic heart failure and may be poorly tolerated due to profound hypotension. Early diagnosis is key, with the aim of targeting the plasma cell responsible for the proliferation of light chains. Chemotherapy with prednisolone and melphalan is used, followed by autologous stem cell transplantation.6 7
A multidisciplinary approach is essential in the management of this aggressive systemic disease.
The profound postural hypotension and intermittent bradycardia would account for the falls experienced by our patient. This case highlights the features of late presentation cardiac AL amyloid and demonstrates the very poor prognosis associated with significant cardiac involvement.
When diagnosed late in the course of their disease, the patient will not be clinically eligible to undertake the required intensive chemotherapy necessary to cure this aggressive disease.
- Amyloid disease may prove difficult to diagnose due to the multiple ways in which it can present and its relative rarity.
- An early diagnosis is paramount, to allow time to institute ‘curative’ therapies.
- In a patient with congestive heart failure and particularly right heart failure in whom systolic function appears adequate, the echo should be carefully examined for diastolic dysfunction and in the case of amyloid cardiomyopathy, a restrictive physiology.
- The combination of low voltage on the ECG and thick walls on echocardiography should alert the physician to the possibility of amyloid heart disease.
- The presence of Q-waves on the ECG, in the absence of any history of myocardial infarction, should raise suspicion as to the presence of amyloid infiltration.