Familial Hypocalciuric Hypercalcemia and Early Severe Aortic Stenosis in A Patient with two Different Heart Failure...

Familial hypocalciuric hypercalcemia (FHH) is a rare hereditary cause of mild hypercalcemia that usually follows a benign clinical course. Calcific aortic stenosis (AS) in a trileaflet aortic valve is uncommon before 65 years of age. Emerging evidence suggests that disturbances in calcium metabolism may contribute to aortic valve calcification.

A 58-year-old woman presented in 2012 with acute heart failure (HF) and left ventricular ejection fraction (LVEF) of 32%. Coronary angiography was normal, and endomyocardial biopsy was not suggestive of myocarditis. She achieved complete recovery with guideline-directed medical therapy, consistent with resolved idiopathic cardiomyopathy. Echocardiography at that time showed only mild aortic valve thickening. She had chronic mild hypercalcemia consistent with FHH, supported by family history, normal parathyroid hormone levels, and fractional excretion of calcium <1%. Genetic testing was negative. During the following decade, progressive aortic valve calcification was documented. In 2023, echocardiography revealed severe AS with a functionally bicuspid valve (peak/mean gradients 105/69 mmHg; valve area 0.5 cm²) and LVEF of 41%, presenting with a second episode of acute HF. She underwent surgical aortic valve replacement with full symptomatic recovery.

This case suggests a possible association between FHH and accelerated valvular calcification leading to premature severe AS. It is also notable for two separate HF episodes caused by different aetiologies: reversible cardiomyopathy initially, followed a decade later by severe AS. Although FHH is generally considered benign, chronic hypercalcemia may justify closer long-term cardiovascular surveillance.

Familial hypocalciuric hypercalcemia may be associated with accelerated valvular calcification and premature severe aortic stenosis.Serial imaging over 10 years documented progression from mild valve thickening to severe calcific aortic stenosis.The case describes two distinct episodes of heart failure caused by different underlying mechanisms.