Atrial Dilated Cardiomyopathy: From Molecular Pathogenesis to Clinical Implications.

Area of Science:

• Cardiology
• Genetics
• Electrophysiology

Background:

• Atrial dilated cardiomyopathy leading to atrial standstill is an ultrarare disorder.
• Characterized by complete loss of atrial electrical and mechanical activity, it carries a high thromboembolic risk.
• The condition presents with absent P waves on ECG and a bradycardic junctional escape rhythm.

Purpose of the Study:

• To elucidate the genetic underpinnings and clinical characteristics of atrial standstill.
• To highlight the importance of early diagnosis and genetic screening for NPPA-related atrial cardiomyopathy.
• To emphasize the need for tailored management strategies, including anticoagulation and pacemaker implantation.

Main Methods:

• Review of clinical cases and genetic analysis.
• Identification and characterization of the homozygous c.449G>A (p.Arg150Gln) mutation in the Natriuretic Peptide A (NPPA) gene.
• Phenotypic description of affected individuals and their heterozygous relatives.

Main Results:

• The homozygous NPPA mutation causes a severe atrial phenotype with biatrial enlargement and progressive atrial inexcitability.
• Heterozygous carriers are typically asymptomatic, underscoring the recessive inheritance pattern.
• Clinical course involves supraventricular arrhythmias, valvular regurgitation, and often requires permanent pacemaker and lifelong anticoagulation.

Conclusions:

• Recognition of atrial standstill as a distinct entity is crucial for timely intervention.
• Genetic screening in patients with unexplained atrial dysfunction can guide precision medicine and improve risk stratification.
• Early diagnosis and management are essential to prevent adverse outcomes in this rare condition.