Aims: Family members with a heritable cardiac conduction system and myocardial disease (chromosome 1p1-1q1) manifest: sinus bradycardia, PR interval prolongation, atrial/ventricular arrhythmias, advanced atrioventricular block, congestive heart failure or sudden cardiac death. A ten family members subset with atrial myopathy/atrial fibrillation was evaluated while in sinus rhythm, prior to the ... [Show full abstract] development of atrial fibrillation. Multidimensional analysis of atrial function in sinus rhythm provided atrial myopathy diagnostic criteria and evaluated left atrial electromechanical function in atrial myopathy/atrial fibrillation family members over time. Methods and Results: A nine-generation pedigree (n=636) was constructed over a 40-year period; of the 325 family members studied, 106 were affected. Multidimensional analyses of electrical, mechanical and electromechanical left atrial function in ten atrial myopathy/atrial fibrillation family members demonstrated: decreased P wave voltage and increased duration, increased left atrial maximal volume, peak acceleration time, pre-ejection period and ejection time. Follow-up (7-10 years) echocardiographic studies in five atrial myopathy/atrial fibrillation family members showed increased left atrial maximal volume, left atrial and left ventricular diameters. Autopsy confirmed atrial myopathy in one atrial myopathy/atrial fibrillation family member with severe biatrial dilatation, atrial cytoplasmic vacuolization, myocyte hypertrophy and interstitial fibrosis. Conclusions: Multidimension left atrial analyses detected atrial myopathy prior to the development of atrial fibrillation, providing an electrophysiological substrate for the subsequent development of heritable atrial fibrillation. Heritable atrial myopathy and heritable atrial fibrillation emerge as phenotypes within the continuum of heritable cardiac conduction system and myocardial disease.