Background: Atrial dilated cardiomyopathy (ADCM) related to homozygous Natriuretic Peptide Precursor A (NPPA) pathogenic variants is an exceptionally rare inherited atrial cardiomyopathy characterized by progressive atrial enlargement, supraventricular arrhythmias, and eventual atrial standstill. Case summary: We report the case of a 9-year-old girl identified through population genetic screening as a homozygous carrier of the NPPA c.449G>A (p.Arg150Gln) variant who subsequently developed symptomatic paroxysmal atrial fibrillation (AF) at the age of 18. Although baseline cardiac investigations were normal, her current evaluation shows biatrial enlargement with preserved ventricular function. She underwent radiofrequency pulmonary vein isolation; however, recurrent symptomatic AF persists, requiring ongoing antiarrhythmic therapy and long-term oral anticoagulation (CHA2DS2-VA: 0; HAS-BLED: 0). Notably, patients with NPPA-related ADCM have a markedly increased thromboembolic risk due to progressive atrial mechanical failure, and anticoagulation should therefore be considered irrespective of conventional clinical risk scores. Discussion and conclusions: This case highlights the importance of genetic testing in young patients with atrial fibrillation and no underlying structural heart disease. The early identification of NPPA-related atrial dilated cardiomyopathy may aid in risk stratification and guide rhythm and anticoagulation management. Expanding genetic screening in select individuals with isolated atrial fibrillation may facilitate earlier diagnosis in this exceptionally rare condition.

Atrial dilated cardiomyopathy with progression to atrial standstill is an ultrarare arrhythmogenic disorder characterized by complete loss of atrial electrical and mechanical activity. This condition, which may occur sporadically or in familial clusters, is associated with a markedly increased thromboembolic risk. The electrocardiographic hallmark is the absence of P waves combined with a bradycardic junctional escape rhythm. Biatrial enlargement gradually evolves into giant atria with preserved biventricular systolic function, while supraventricular arrhythmias and progressive atrial inexcitability dominate the clinical course. Valvular regurgitation frequently worsens in parallel with atrial remodelling, and patients often require permanent pacemaker implantation as well as lifelong anticoagulation. Among the few genetic determinants identified, the homozygous c.449G>A (p.Arg150Gln) mutation in the Natriuretic Peptide A gene represents one of the best characterized mechanisms. Disertori et al. first reported this pathogenic variant in 13 affected individuals from Italian families, establishing a recessive inheritance pattern. More recently, Silva et al. and Forleo et al. described additional cases, expanding the phenotypic spectrum of NPPA-related atrial cardiomyopathy. These findings confirm that homozygous carriers develop a severe atrial phenotype, whereas heterozygous relatives typically remain asymptomatic, underlining the importance of genetic testing in young patients with unexplained atrial fibrillation or standstill. Recognition of atrial cardiomyopathy as a distinct clinical entity is crucial, since early diagnosis may guide timely anticoagulation, arrhythmia management, and tailored follow-up. Broader adoption of genetic screening in patients with isolated atrial dysfunction could support precision medicine approaches, improve risk stratification, and ultimately prevent adverse outcomes in this ultrarare but highly morbid condition.

Atrial standstill is a rare arrhythmogenic disorder characterized by complete atrial electrical and mechanical inactivity. We report the 15th documented case of atrial dilated cardiomyopathy associated with the homozygous c.449G>A (p.Arg150Gln) NPPA mutation. A 31-year-old woman presented with persistent atrial fibrillation, biatrial enlargement, and junctional rhythm. Electrophysiological studies confirmed atrial inexcitability. Despite preserved ventricular function, she required permanent His-bundle pacing. Genetic testing later revealed a homozygous NPPA mutation, whereas heterozygous family members remained asymptomatic. This case highlights the diagnostic value of genetic testing in young patients with atrial fibrillation and no structural heart disease. Early recognition of NPPA-related atrial dilated cardiomyopathy may guide arrhythmia management and anticoagulation strategies, reducing thromboembolic risk. Broader implementation of genetic screening in selected individuals with isolated atrial dysfunction may support earlier diagnosis, personalized treatment, and better outcomes in this ultrarare condition.

Myocarditis typically affects ventricles, whereas isolated atrial myocarditis is rare, causing conduction abnormalities, atrial standstill, and right heart failure. Two weeks after a respiratory infection, a 35-year-old man developed dyspnea, leg edema, and bradycardia. Electrocardiogram revealed a narrow QRS escape rhythm without P waves, and N-terminal pro-B-type natriuretic peptide was elevated. Echocardiography showed severe right ventricular dysfunction with massive tricuspid regurgitation. Cardiac magnetic resonance demonstrated atrial late gadolinium enhancement and mild edema, whereas electrophysiological testing confirmed atrial standstill and atrioventricular block. This case highlights isolated atrial myocarditis as a rare cause of atrial dysfunction, marked by postcapillary pulmonary hypertension and prominent V waves, despite normal mitral valves. Rapid atrial fibrosis progression resulted in silent atria, confirmed by magnetic resonance imaging and electrophysiology. Further research is required to clarify pathophysiology and establish effective management. Isolated atrial myocarditis is a rare cause of atrial standstill and atrioventricular block. Comprehensive multimodality imaging is essential for accurate diagnosis and management.

Emery-Dreifuss muscular dystrophy (EDMD) is a rare inherited syndrome that affects muscles, joints, and the heart. The classic clinical triad includes early joint contractures, slowly progressive muscle weakness, and cardiac abnormalities. The common cardiac manifestations include conduction disturbances, systolic dysfunction, and dilated cardiomyopathy and may be associated with left ventricular noncompaction with an increased risk of thromboembolic events. Conduction disturbances include atrial arrhythmias, atrial standstill, complete heart block, or ventricular tachyarrhythmia. Cardiac magnetic resonance imaging (CMR) can help in the diagnosis of this condition by identifying chamber dilatation, systolic dysfunction, and late gadolinium enhancement of the atrium. Additional MRI finding of paraspinal muscle atrophy, an important finding in this muscular dystrophy, helped in reaching a confident imaging diagnosis. Our case in this article highlights the clinical and CMR findings of this rare condition.