Systemic cardiac amyloidosis was until 2018 a disease only open to symptomatic treatment with typical survival after diagnosis of only a few years. Tafamidis was the first treatment for transthyretin amyloid cardiomyopathy which is a predominant cause of serious systemic cardiac amyloidosis. Treatment should be commenced as early as possible in the disease, which is challenging to diagnose. Cardiac amyloid can be confined to the conducting system where it manifests itself as complete heart block which is treatable by pacing and has a different prognosis to a cardiomyopathy.
Transthyretin amyloid cardiomyopathyCardiac amyloidosis due to transthyretin deposition can be found in those with either the autosomal dominant transthyretin familial amyloid polyneuropathy genotype ( ATTRm ) which typically manifests after the third decade or as a rare diagnosis in those over 60 with heart failure due to senile systemic amyloidosis (ATTRwt)
Genetics and pathophysiology
See transthyretin, as misfolded monomers or oligomers are deposited in the myocardium.
Presently not fully understood due to gross under diagnosis. There are over 120 mutations of transthyretin known with variable phenotype. Senile systemic amyloidosis tends to be diagnosed in males over 60. Genetic studies have not been practical given the multiple mutations, but in this age group the development of a labelled nuclear scan has resulted in adequate sensitivity and specificity. On this basis there is a prevalence of over 10% in patients with heart failure with a preserved ejection fraction and over 15% in patients undergoing transcatheter aortic-valve replacement for severe aortic stenosis. The incidence is 5% among patients with hypertrophic cardiomyopathy.
Cardiomyopathy and symptoms of heart failure:
- Postural hypotension
- Bundle branch block, atrioventricular block, sinoatrial disease
- Atrial fibrillation
- Suspect in patients with inherited polyneuropathy
- Genetic screening
- Consider nuclear medicine amyloid scan in those with:
- Characteristic echo findings
- Heart failure with a preserved ejection fraction
- Severe aortic stenosis
Prior to specific treatment mean survival from cardiac symptom presentation was less than 3 and a half years. In the classic inherited form, it was less than two and a half years. Current treatment options are unlikely to benefit in terms of lifespan those diagnosed late and in more than NYHA grade III heart failure although symptoms might benefit. This is as tafamidis only impacts after 18 months in terms of survival.