# The High Price of Interrupted Follow‐Up: Catastrophic Progression of Homozygous Familial Hypercholesterolemia—A Case Report and Literature Review

## TL;DR

A young woman with homozygous familial hypercholesterolemia faced severe heart failure and death due to interrupted medical care during the pandemic.

## Contribution

Highlights the catastrophic consequences of disrupted follow-up in homozygous FH patients and emphasizes the need for continuous monitoring.

## Key findings

- Homozygous FH can lead to fatal heart failure despite maximal lipid-lowering therapies.
- Interrupted follow-up during the pandemic resulted in severe cardiovascular deterioration.
- Early detection and sustained multidisciplinary care are critical for managing HoFH.

## Abstract

Familial hypercholesterolemia (FH) is the most common monogenic lipid disorder, primarily resulting from mutations in LDLR, APOB, and PCSK9 genes. These mutations cause persistently high levels of low‐density lipoprotein cholesterol (LDL‐C), predisposing affected individuals to premature atherosclerotic cardiovascular disease (ASCVD). Homozygous FH (HoFH), a rare but severe form, manifests early in life with cutaneous xanthomas and accelerated coronary and aortic disease. Early diagnosis and aggressive, lifelong management are crucial, yet challenges remain, particularly when follow‐up is interrupted. We report the case of a 20‐year‐old female diagnosed with HoFH at age 13 after presenting with xanthomas. Initial evaluation revealed mild to moderate aortic stenosis and early coronary artery involvement. Genetic testing confirmed a homozygous LDLR mutation. Despite treatment with atorvastatin and evolocumab, partial lipid control was achieved, and follow‐up was disrupted during the COVID‐19 pandemic. At 20 years, she presented with worsening dyspnea, paroxysmal nocturnal dyspnea, and orthopnea. Advanced imaging documented severe heart failure with an ejection fraction of 20%, significant ventricular dilation, severe mitral regurgitation, and calcified aortic stenosis. Coronary angiography demonstrated critical coronary stenoses, while subsequent adjustments in her lipid‐lowering regimen, including rosuvastatin, ezetimibe, increased evolocumab dosing, and bempedoic acid, failed to stabilize her condition. Despite recommendations for surgical intervention, the patient's critical status precluded operative management, and she tragically died on the day of her scheduled follow‐up. This case underscores the aggressive natural history of HoFH and the dire consequences of interrupted follow‐up care. Early detection and sustained, multidisciplinary management are essential to mitigate rapid cardiovascular deterioration in HoFH patients. Consistent monitoring and prompt therapeutic adjustments remain pivotal in improving outcomes and reducing the high mortality risk associated with advanced aortic and coronary complications in these patients.

Homozygous familial hypercholesterolemia can progress to fatal, multi‐valvular and coronary disease in early adulthood despite maximal lipid‐lowering therapy, including statins, ezetimibe, PCSK9 inhibition, and bempedoic acid. Continuous follow‐up is indispensable to detect rapid deterioration and enable timely interventions that may alter the otherwise catastrophic course.