Storage diseases with hypertrophic cardiomyopathy phenotype

Abstract

Never judge a book by its cover, nor assume hypertrophic cardiomyopathy (HCM) as sarcomeric, as appearances can deceive. HCM phenocopies account for a 5-10% of the cases, mainly represented by storage diseases, flagged by the increasing prevalence of senile cardiac amyloid in developing countries. Multisystemic and heterogeneous presentation of these entities is a challenge for clinicians, and time delay in diagnosis is a major concern. Promising drugs and gene-specific tailored therapies are under development, therefore, more than ever, appropriate understanding of these conditions is mandatory for adequate early treatment and counselling. In this review, storage disorders will be classified as extracellular and intracellular deposit storage diseases, focusing our attention on the most prevalent conditions from the cardiologist's perspective.

Figure 1.. Spectrum of association genotype-phenotype in familiar ATTR, proposed by Rapezzi et al.

From isolated peripheral neuropathy (V30M) to predominant cardiac phenotype (V122L) (modified from 13).

Figure 2.. Diagnostic work-up algorithm.

(DPD, (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD); MPS, monoclonal protein studies).

Figure 3.. See the disproportionate prominence of contracted biceps, a result of distal biceps tendon non-traumatic rupture.

Figure 4.. Typical electrocardiographic findings, showing atrial fibrillation, low voltages and pseudoinfarct pattern.

Male patient, 86 years-old.

Figure 5.. 2-dimensional echocardiographic images of a patient with ATTR-CA.

Concentric LVH is visible in the first on the left and in the image in the middle. Ground glass appearance of the myocardium is also apparent. In the image on the right hand side we can appreciate interventricular septum thickening (white arrow) and valve thickening.

Figure 6.. Diastolic dysfunction in early stages, shown by E/A relation <1 in Doppler wave mitral inflow velocities.

Figure 7.. Low velocities in tissue Doppler imaging of the mitral annulus (under 8 cm/s) can be seen in early stages.

Figure 8.. Abnormal ventricular strain and strain rate, typically with apical sparing.

Apical Strain/ Basal Strain >2.1.

Figure 9.. Restrictive physiology.

In the image on the left, E wave high velocities measured in the mitral inflow with very low A wave velocities with abnormal deceleration time, indicates high left atrial pressure and poor compliant left ventricle. On the right hand side, the pulmonary vein Doppler velocities show absence of systolic inflow wave and high diastolic velocities, consistent with restrictive physiology as well.

Figure 10.. Bisphosphonate scintigraphy.

Grade 3 uptake score in a patient with ATTR-CA.

Figure 11.. Electrocardiogram of a 20 year-old male patient with classic form of AFD.

Sinus rhythm and short PR interval is patent. Repolarization abnormalities with T wave inversion in V3 to V6 and I an AVL is also present.

Figure 12.. Red Flags and life-time relation.

The chart shows the approximate onset of the symptoms and duration. Hypohidrosis, gastrointestinal symptoms and neuropathic pain, in some patients may disappear with age.

Figure 13.. Renal biopsy under electron microscopy showing the typical zebra body, formed by Gb3 deposit in the lysosome (white arrow).

Figure 14.. Algorithm for diagnostic work-up.

Figure 15.. ECG showing pre-excitation pattern and high voltages with T-wave inversion.

Concentric left ventricular hypertrophy is present in two thirds of the patients, usually with impaired diastolic function and some with restrictive pattern. Ejection fraction is generally preserved, occasionally with LVOT obstruction. It is also reported the progression to dilated cardiomyopathy. Supraventricular arrhythmias are frequent (38%) mainly atrial flutter and atrial fibrillation. In two thirds of cases there is a form of bradyarrhythmia (AVB or sinus dysfunction) that may need pacemaker implantation. Sudden cardiac death, although rare, can be a form of presentation in a range of 12 to 20% of the patients.