7th March 2024

Restrictive Cardiomyopathy

Pathology

Restrictive cardiomyopathy (RCM) is an umbrella term for pathologies in which there is increased stiffness of the myocardium, leading to increased pressure with only small increases in volume. It is thought to be one of the least common forms of cardiomyopathy.

A number of pathologies can lead to restrictive physiology; Genetic causes include troponin I abnormalities, familial amyloidosis, and Fabry’s disease, while acquired causes can include light chain amyloidosis, drug induced RCM, carcinoid syndrome, anthracycline chemotherapy and radiation. Haemochromatosis can be either genetically inherited through the HFE gene or acquired through repeated blood transfusions, as can sometimes be seen in thalassaemia.

It has previously been taught that systolic function is preserved in patients with these disorders, but contraction is rarely normal in these conditions and abnormalities of systolic function can be demonstrated on myocardial deformation imaging.

Signs and symptoms

RCM leads to increased myocardial stiffness. By the time of diagnosis, this has usually led to typical signs of heart failure described above, such as dyspnoea, fatigue, and pulmonary and peripheral oedema, but due to the increased ventricular stiffness on examination, you may also hear a loud third heart sound, due to abrupt cessation of rapid ventricular filling.

A majority of patients with RCM will also develop atrial fibrillation due to elevated filling pressures and subsequent left atrial enlargement, the latter of which is strongly correlated with the presence of atrial fibrillation. This will lead to the presence of an irregularly irregular pulse and may lead to patients experiencing palpitations alongside worsening dyspnoea and presyncope.

RCM is most commonly idiopathic in nature, with amyloidosis being the most common identifiable cause. If amyloid is discovered, then the patient may manifest other signs and symptoms of the underlying pathology, such as features of myeloma in AL amyloid, signs of iron deposition such as a change in skin colour and liver failure in haemochromatosis or carpal tunnel syndrome due to systemic amyloid deposition.

Investigations

Echocardiography will typically show thickened myocardium and thickened valves with small ventricular cavity sizes. It will also demonstrate impaired filling with diastolic dysfunction due to impaired relaxation caused by the increase in myocardial stiffness.

ECG findings in RCM will typically include low voltage QRS complexes, as well as varying blocks including bundle branch block or complete heart block. Atrial fibrillation is common and, thus, this may also be seen on the ECG. You may also see ‘pseudo-infarction’ Q waves present.

RCM is typically idiopathic in nature, though amyloid is the commonest identifiable cause in the western world. Other causes can include Sarcoidosis and infiltrative diseases such as haemochromatosis or Fabry’s disease.

Sarcoid would be suggested by the presence of systemic granulomas seen on imaging with elevated serum ACE levels and hypercalcaemia. Fabry’s can be diagnosed by assessing for low levels of alpha-galactosidase A on blood tests. Haemochromatosis can be diagnosed through assessment of ferritin and transferrin saturation, while suspicion of a genetic inheritance should lead to assessment for mutation of the HFE gene.

Given that amyloid is a significant and treatable cause of RCM, its presence or absence should be investigated. There are two commonly acquired types, AL and AA amyloid – the former caused by light chain deposition and the latter by overproduction of acute phase proteins, typically in chronic inflammation. AL more commonly affects the heart and is the more common of the two subtypes.

Investigation for AL amyloid should include a myeloma screen with protein electrophoresis and urinary Bence-Jones protein analysis. 

Investigation for AA amyloid include amyloid scintigraphy (a nuclear imaging modality) to assess organ distribution, while fat biopsy can confirm presence when it demonstrates red-green birefringence under polarised light after staining with congo red.

Transthyretin amyloidosis is the most common inherited systemic form of amyloidosis and if suspected after imaging tests then genetic testing can be performed.

Treatment

If an underlying disease process is found which is amenable to treatment then this can be actively targeted. Unfortunately, in many cases, the underlying pathology is not responsive to treatment.

In the absence of an identifiable cause, then, the treatment is largely based upon symptoms; cardiac transplantation can be considered in certain patients, particularly the young, while optimal medical therapy is given for heart failure with reduced ejection fraction as described above for DCM.  Atrial fibrillation is a very common consequence due to the elevated left atrial pressures so often rate control and anticoagulation are employed.

Pacemakers can be considered in those with conduction system disease, whilst implantable cardioverter defibrillators can be provided in high-risk patients.

References

• https://patient.info/doctor/restrictive-cardiomyopathy
• https://www.ahajournals.org/doi/full/10.1161/circresaha.117.310982
• https://www.hindawi.com/journals/rrp/2017/2874902/