Cardiac phenotype of propionic acidemia in the Amysh community

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Propionic acidemia (PA) is an organic acid disorder with poorly described cardiac phenotype despite progressive important cardiac remodeling and causes of death including congestive heart failure and sudden cardiac death, often in a setting of vigorous exercise or stress. Cardiac modifications begin at cellular level, both metabolic and lipid depositions, resulting in overall changes in shape, size, geometry and function, with ventricular dysfunction and risk for arrhythmias at young age. Purpose Echocardiographic assessment of left ventricular (LV) shape and timing (especially the Isovolumic contraction time (IVCT)) can help us understand the pathophysiology during the remodeling process in this rare disease. Methods We included all the PA patients from the Amish plain Community seen in our center. Clinical data, including demographics, ECG and echo measurements were recorded. Results We included 22 patients, who were homozygous for the pathogenic variant for PA, (59% males, 20.3± 13.3 years old). ECG analysis showed mild tachycardia (92 ± 30bpm) with normal QRS (84± 18 msec) and QTc segments duration (424± 31 msec). Echocardiography demonstrated a globular LV with dilated base and apical segments, normal systolic function, and normal diastolic function. The Global Longitudinal Strain was mildly decreased (GLS −17±3.08) with a dispersion of the regional strain with apical sparing. (Figure 1). The mean LV IVCT (75 msec) was longer compared to mean RV IVCT (69 msec, Figure 1). Conclusion Patients with PA present with very specific remodeling, including an increase in sphericity of the heart and slightly decreased GLS with normal EF. The very long LV IVCT suggests a problem with pressure generation, potentially as a marker of decreased LV contractility, either at cellular level or with activation-contraction coupling. Together with the difference in timings between the LV and RV this might become a substrate for life-threatening arrhythmias. A contractility problem, together with the exercise induced arrhythmias suggest that PA patients might benefit from afterload reduction.