Key Clinical Updates in Restrictive Cardiomyopathy
Tafamidis helps prevent the misfolding of the TTR tetramer and is approved for treatment.
Patisirin is also available, and it inhibits both variant and wild type TTR production.
For the variant TTR polyneuropathy, subcutaneous inotesin is available (it binds to TTR mRNA preventing transcription).
ESSENTIALS OF DIAGNOSIS
Right heart failure tends to dominate over left heart failure.
Pulmonary hypertension is present.
Amyloidosis is the most common cause.
Echocardiography is key to diagnosis.
Radionuclide imaging or myocardial biopsy can confirm amyloid.
Restrictive cardiomyopathy is characterized by impaired diastolic filling with reasonably preserved LV chamber size (VIDEO 10–25). The condition is relatively uncommon, with the most frequent cause being amyloidosis. The diagnosis of cardiac amyloidosis has dramatically increased in the last few years since diagnostic testing has improved and there is an awareness of its prevalence. The prevalence of AL amyloid is approximately 12 cases per million, the prevalence of variant or hereditary ATTR amyloid is about 0.3 cases per million, and the prevalence of wild type ATTR amyloid is 155–191 cases per million. Many experts believe the actual prevalence of wild type ATTR is much higher. While light-chain amyloid proteins can be toxic to cardiomyocytes, they may also internalize into many cell types and this may explain some of the cardiac dysfunction observed. ATTR refers to transthyretin, a protein normally found in the liver that helps transport thyroid hormones and vitamin A. Wild type (normal) occurs more commonly in the elderly and in men, and previously was referred to as “senile systemic amyloidosis.” Hereditary or variant ATTR is genetically transmitted, deposition occurs at an earlier age, and it has associated neurologic impact. TTR is a tetramer that can dissociate into four monomers and aggregate as amyloid fibrils. The differential diagnosis of a restrictive cardiomyopathy includes infiltrative disorders beside amyloidosis, such as sarcoidosis, Gaucher disease, and Hurler syndrome. Storage diseases such as hemochromatosis, Fabry disease, and glycogen storage diseases can also produce the picture. Noninfiltrative diseases, such as familial cardiomyopathy and pseudoxanthoma elasticum, can be implicated rarely, and other secondary causes include diabetes, systemic sclerosis (scleroderma), radiation, chemotherapy, CAD, and longstanding hypertension.
Video 10-25: Restrictive cardiomyopathy on pulse wave doppler examination.
(Used, with permission, from B Macrum and E Foster.)
Concentric LVH usually results in an increase in the LVEF via the law of Laplace where wall thickness is inversely proportional to wall tension. In restrictive cardiomyopathy the walls are thickened, but the LVEF is lower; this is often a clue to the presence of an infiltrative process.
Restrictive cardiomyopathy must be distinguished from constrictive pericarditis (see Table 10–15). The key feature is that ventricular interaction is accentuated with respiration in constrictive pericarditis...