Clinical impact of post-mortem genetic testing in cardiac death and cardiomyopathy.

Post-mortem genetic analyses may help to elucidate the cause of cardiac death. The added value is however unclear when a cardiac disease is already suspected or affirmed. Our aim was to study the feasibility and medical impact of post-mortem genetic analyses in suspected cardiomyopathy. We studied 35 patients with cardiac death and suspected cardiomyopathy based on autopsy or clinical data. After targeted sequencing, we identified 15 causal variants in 15 patients (yield 43%) in sarcomeric (n = 8), desmosomal (n = 3), lamin A/C (n = 3) and transthyretin (n = 1) genes. The results had various impacts on families, i.e. allowed predictive genetic testing in relatives (15 families), planned early therapeutics based on the specific underlying gene (5 families), rectified the suspected cardiomyopathy subtype (2 families), assessed the genetic origin of cardiomyopathy that usually has an acquired cause (1 family), assessed the diagnosis in a patient with uncertain borderline cardiomyopathy (1 family), reassured the siblings because of a de novo mutation (2 families) and allowed prenatal testing (1 family). Our findings suggest that post-mortem molecular testing should be included in the strategy of family care after cardiac death and suspected cardiomyopathy, since genetic findings provide additional information useful for relatives, which are beyond conventional autopsy.

Occurrence of significant long PR intervals in patients implanted for sinus node dysfunction and monitored with SafeR™: The PRECISE study.

BACKGROUND: Long PR intervals may increase cardiovascular complications, including atrial fibrillation. In pacemakers, the SafeR™ mode monitors PR intervals, switching from AAI to DDD when criteria for atrioventricular block are met. AIMS: The PRECISE study evaluated the incidence and predictors of long PR intervals and their association with incident atrial fibrillation after 1 year in patients implanted for sinus node dysfunction and free from significant conduction disorders at baseline. METHODS: This French, prospective, multicentre, observational trial enrolled patients implanted with a REPLY™ dual-chamber pacemaker. Pacemaker memory recorded long PR intervals (defined as first-degree atrioventricular block mode switches occurring after six consecutive PR/AR intervals≥350/450ms) and atrial fibrillation incidence (fallback mode switch>1minute/day). Predictors were identified from baseline variables (age, sex, AR and PR intervals, atrial rhythm disorder and medication) using logistic regression. RESULTS: Of 291 patients with sinus node dysfunction enrolled, 214 were free from significant conduction disorders at baseline (mean age 79±8 years; 44% men; PR/AR intervals<350/450ms). After 1 year, long PR intervals had occurred in 116 patients (54%) and atrial fibrillation in 63 patients (30%). Amiodarone was the only independent predictor of long PR interval occurrence (odds ratio 2.50, 95% confidence interval 1.20-5.21; P=0.014). There was a strong trend towards an association between long PR interval and atrial fibrillation incidence (odds ratio 1.86, 95% confidence interval 0.97-3.61; P=0.051). CONCLUSIONS: Half of the patients with pure sinus node dysfunction developed long PR intervals in the year following pacemaker implantation. Amiodarone was the only independent predictor of long PR intervals. There was a strong trend towards an association between long PR intervals and incident atrial fibrillation.

Coxiella burnetii endocarditis on bioprosthetic aortic valve, with peripheral arterial embolism.

Acute limb ischemia related to Coxiella burnetii endocarditis is rare. We report an original case of a 68-year-old man hospitalized for recurrent acute left limb ischemia in a context of atrial flutter, which revealed C. burnetii endocarditis. This case illustrates that even if embolic events are uncommon, septic embolisms must be systematically searched for in case of C. burnetii endocarditis. Conversely, extensive etiologic explorations must be performed in case of systemic embolism. New molecular techniques represent a major step forward in infective endocarditis diagnosis. Finally, diagnosis must be suspected in case of unexplained fever, inflammatory syndrome, or embolic event, especially in patients at risk. Conversely, in case of chronic Q fever, an immunodeficiency cause must be researched.