Familial restrictive cardiomyopathy

Affected individuals usually have symptoms of progressive left- and right-sided heart failure, with an especially poor prognosis in early-onset disease. Presenting features may include:

• fatigue;
• breathlessness;
• peripheral oedema;
• electrocardiogram (ECG) results that show low-voltage QRS complexes, widespread flattening of T-waves, conduction disease and arrhythmias;
• progressive, often bi-atrial, dilation, which is common and can be striking (atrial fibrillation may be associated with abrupt and marked haemodynamic decompensation);
• pulmonary hypertension and cirrhosis, which can complicate the clinical course and restrict therapeutic options; and/or
• variable cardiac MRI and/or echocardiography imaging findings that include atrial dilation and parameters of diastolic dysfunction. There is also the possibility of a small left ventricular (LV) cavity with normal ejection fraction, mild increases in LV wall thickness and late enhancement.

Other heart diseases that can result in restrictive or constrictive heart physiology (such as amyloidosis or pericardial disease respectively) should also be considered. Their exclusion, alongside a positive family history, is a crucial part of the evaluation of suspected familial restrictive cardiomyopathy (RCM).

• Only a few pathogenic variants have been identified in familial RCM, the majority of which are in the sarcomeric protein genes that are also implicated in hypertrophic cardiomyopathy (HCM).
• TNNI3 variants are the most common genetic cause of familial RCM. However, variants in the TNNI2, MYH7, FLNC and DES genes (often associated with conduction disease) are also a possible cause.
• Genomic testing for familial RCM should only be considered with the involvement of a specialised inherited cardiac conditions service and after consultation with clinical genetics services. Testing for another cardiomyopathy condition (such as HCM) should be considered if there are features of that condition, even if they are subtle.

Familial RCM usually demonstrates an autosomal dominant pattern of inheritance.

Management of RCM depends on clinical presentation and may include:

• pharmacological therapy, mainly for heart failure (diuretics and ACE inhibitors) and arrhythmias (beta-blockers and anticoagulants);
• pacemaker implantation for conduction disease; or
• heart transplant for severe heart failure symptoms.

For clinicians

• Cardiomyopathy UK: Restrictive cardiomyopathy
• NHS England: National Genomic Test Directory

References:

• Rapezzi C, Aimo A, Barison A and others. ‘Restrictive cardiomyopathy: Definition and diagnosis‘. European Heart Journal 2022: volume 43, issue 45, pages 4,679–4,693. DOI: 10.1093/eurheartj/ehac543

For patients

• Cardiomyopathy UK: Restrictive cardiomyopathy