CJ Petrie, M MacDonald,
MM Lindsay.
Department of Cardiology, Western Infirmary,
Glasgow, G11 6NT
Correspondence:
Dr Colin J Petrie, Department of Cardiology,
Western Infirmary, Glasgow G11 6NT,
United Kingdom
E-mail: colinjamespetrie@yahoo.co.uk
SMJ 2007 52(4): 54
We present a 72-year-old man with worsening cardiac failure, atrial
fibrillation and recurrent syncope precipitated by the prescription of digoxin.
Neurocardiogenic syncope was diagnosed however the patient died prior to
definitive treatment. Post-mortem revealed primary amyloid as the unifying
diagnosis.
Keywords: Heart failure, atrial fibrillation,
neurocardiogenic syncope, digoxin, amyloidosis.
Chronic heart failure is a frequent cause of hospital admission in the
elderly population with coronary artery disease being the commonest aetiology.
Atrial fibrillation with a rapid ventricular response is a common complication
and is often successfully treated with digoxin. Amyloidosis is a rare cause of
heart failure, and must be borne in mind as a potential diagnosis due to the
important treatment implications.
A 72-year-old man was admitted to hospital with progressive dyspnoea over
the preceding six months. His relevant past medical history was of hypertension
and diabetes mellitus. On admission he was in atrial fibrillation, with a rapid
ventricular response and Killip class III heart failure.
Serum creatinine was normal. Resting ECG demonstrated atrial
fibrillation, anteroseptal Q waves and non-specific ST depression in V4-V6 (see Figure
1). Trans-thoracic echocardiography demonstrated concentric left ventricular
hypertrophy, a globally hypokinetic but undilated left ventricle and a dilated
right heart with pulmonary hypertension (see Figure
2). An exercise test had been performed some weeks previously, which
demonstrated ECG changes at low workload consistent with inducible myocardial
ischaemia. We therefore proceeded to coronary angiography which surprisingly
revealed normal coronary arteries. Treatment included intravenous diuretics,
angiotensin converting enzyme inhibition and digoxin. Initially his fluid
overload was resistant to therapy requiring intravenous dopamine and oral
metolazone as adjuvant treatments to establish a satisfactory diuresis.
Following oral digoxin therapy he developed disabling recurrent pre-syncopal
episodes characterised by a relative bradycardia (heart rate 40-50/min) (see Figure
3) and hypotension. Heart rhythm remained as atrial fibrillation. These
episodes generally resolved on assuming the supine position. Continuous holter
monitoring did not reveal significant brady-arrhythmia and serum digoxin levels
were normal. We made the presumptive diagnosis of neurocardiogenic syncope with
combined vasomotor and cardio-inhibitory components. Beta-blockade was
introduced but unfortunately on the day of his planned pacemaker insertion he
had a witnessed pulseless electrical activity (PEA) cardiac arrest. The rhythm
remained as atrial fibrillation but resuscitation was unsuccessful.
At post mortem he had bi -ventricular enlargement (cardiac weight 560
grams) and microscopic examination revealed primary AL amyloidosis with
extensive cardiac involvement. Immunohistochemistry suggested a final diagnosis
of amyloid light chain, restricted to lambda type.
AL amyloidosis (previously called primary amyloid) is derived from light-
chain immunoglobulin produced by monoclonal plasma cells. These light chains
deposit most frequently in the kidney and the heart. Cardiac involvement in
primary amyloidosis may lead to a dilated cardiomyopathy, with predominant
systolic dysfunction, or a restrictive cardiomyopathy. ECG abnormalities are
common, including arrhythmias and atrio-ventricular block.1
Predominant right sided heart failure is the most common clinical feature and
coronary heart disease is often incorrectly diagnosed.2
Sensory and autonomic neuropathy are relatively common features and the
latter may be severe, resulting in symptomatic hypotension.3
Untreated AL amyloid has a median survival of only 1-2 years, with cardiac
involvement predicting the worst outcome.4 The symptoms of
amyloidosis and heart failure are often non specific including general lethargy
and reduced exercise tolerance. In most cases cardiac amyloidosis is diagnosed
predominantly after death.2
With a history of diabetes, hypertension, a positive exercise test and an
abnormal echocardiogram, a presumptive diagnosis of ischaemic cardiomyopathy was
made. Digoxin seemed a logical therapy in a man with heart failure and atrial
fibrillation. However, there is a reported enhanced sensitivity to digoxin,
possibly due to irreversible binding of digoxin to the amyloid fibrils in the
myocardium.6, 7 The temporal sequence of events were such that his
recurrent syncope and hypotensive episodes (approximately 13 in total) started
after digoxin was commenced and appears to have had an important aetiological
role. Lying and standing blood pressures at times of pre-syncope were not done
routinely, as immediate management involved lying him flat.
We tried to avoid excessive diuresis by ensuring weight loss of no more
than 1kg/day. Of considerable interest is that at cardiac catheterisation he
experienced a similar episode. With intra-arterial (via a right femoral arterial
sheath) pressure monitoring his blood pressure dropped, initially with a fall in
heart rate. However the heart rate reduction was modest (approximately 40/min)
and with atropine the heart rate increased but with no appreciable subsequent
rise in blood pressure. Even with a heart rate of 80/min his invasive systolic
blood pressure was only 50 mmHg. Blood pressure continued to fall (but rhythm
remained atrial fibrillation) resulting in a PEA arrest. On this occasion he was
resuscitated with fluid and adrenaline. There was no evidence of coronary
ischaemia/abrupt vessel closure/air embolism/vessel dissection or anaphylaxis
during the angiogram and he was haemodynamically stable at the end of the
procedure.
We did not perform a tilt table test (specifically to look for
cardio-inhibitory episodes or a vasodepressor response) as we thought a
pacemaker was warranted. This investigation can been useful, even after
pacemaker implantation, to try and tease out which components are more crucial
in determining hypotensive episodes. We concluded that the hypotension was
secondary to a mixed picture of bradycardia and vasodilatation, but
predominantly the latter. Recognition that digoxin treatment can have an adverse
outcome in such patients is important.
Heart failure and atrial fibrillation are both common and cardiac
amyloidosis is rare. However, the recognition that digoxin can be deleterious in
this condition, may lead clinicians to a greater awareness of both cardiac
amyloid as a potential diagnosis, and the avoidance of cardiac glycosides in
this condition.
Learning Points
AL amyloid presents non-specifically,
depending on the organ(s) involved. Cardiac involvement is common and
carries a poor prognosis.
Coronary artery disease is often
mistakenly diagnosed because of non specific electrocardiographic findings,
anginal symptoms and echocardiographic abnormalities. The diagnosis is
frequently made at post mortem.
Autonomic involvement is common in AL
amyloid, but the pathophysiology of blood pressure abnormalities is poorly
understood.
Digoxin therapy is contraindicated in cardiac amyloidosis and when unexplained symptomatic deterioration occurs after digoxin therapy, one should have a high index of suspicion of underlying cardiac amyloid.
References
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2. Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med. 1997;25;337(13):898-909.
3. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol. 1995;32(1):45-59.
4. Khan MF, Falk RH. Amyloidosis.Postgrad Med J. 2001:77(913):686-93. Review.
5. Gertz MA, Falk RH, Skinner M, Cohen AS, Kyle RA. Worsening of congestive heart failure in amyloid heart disease treated by calcium channel-blocking agents. Am J Cardiol. 1985 ;55:1645.
6. Spyrou N, Foale R. Restrictive cardiomyopathies. Curr Opin Cardiol. 1994.9:344-8.
7. Rubinow A, Skinner M, Cohen AS. Digoxin sensitivity in amyloid cardiomyopathy. Circulation. 1981;63(6):1285-8.