Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy.

BACKGROUND: The genetic cause of hypertrophic cardiomyopathy remains unexplained in a substantial proportion of cases. Formin homology 2 domain containing 3 (FHOD3) may have a role in the pathogenesis of cardiac hypertrophy but has not been implicated in hypertrophic cardiomyopathy. OBJECTIVES: This study sought to investigate the relation between FHOD3 mutations and the development of hypertrophic cardiomyopathy. METHODS: FHOD3 was sequenced by massive parallel sequencing in 3,189 hypertrophic cardiomyopathy unrelated probands and 2,777 patients with no evidence of cardiomyopathy (disease control subjects). The authors evaluated protein-altering candidate variants in FHOD3 for cosegregation, clinical characteristics, and outcomes. RESULTS: The authors identified 94 candidate variants in 132 probands. The variants' frequencies were significantly higher in patients with hypertrophic cardiomyopathy (74 of 3,189 [2.32%]) than in disease control subjects (18 of 2,777 [0.65%]; p < 0.001) or in the gnomAD database (1,049 of 138,606 [0.76%]; p < 0.001). FHOD3 mutations cosegregated with hypertrophic cardiomyopathy in 17 families, with a combined logarithm of the odds score of 7.92, indicative of very strong segregation. One-half of the disease-causing variants were clustered in a small conserved coiled-coil domain (amino acids 622 to 655); odds ratio for hypertrophic cardiomyopathy was 21.8 versus disease control subjects (95% confidence interval: 1.3 to 37.9; p < 0.001) and 14.1 against gnomAD (95% confidence interval: 6.9 to 28.7; p < 0.001). Hypertrophic cardiomyopathy patients carrying (likely) pathogenic mutations in FHOD3 (n = 70) were diagnosed after age 30 years (mean 46.1 ± 18.7 years), and two-thirds (66%) were males. Of the patients, 82% had asymmetric septal hypertrophy (mean 18.8 ± 5 mm); left ventricular ejection fraction <50% was present in 14% and hypertrabeculation in 16%. Events were rare before age 30 years, with an annual cardiovascular death incidence of 1% during follow-up. CONCLUSIONS: FHOD3 is a novel disease gene in hypertrophic cardiomyopathy, accounting for approximately 1% to 2% of cases. The phenotype and the rate of cardiovascular events are similar to those reported in unselected cohorts. The FHOD3 gene should be routinely included in hypertrophic cardiomyopathy genetic testing panels.

Anatomical classification of left atrial appendages in specimens applicable to CT imaging techniques for implantation of amplatzer cardiac plug.

BACKGROUND: Certain anatomical characteristics of the left atrial appendage (LAA) are associated with complexity in the implantation of occluder devices. OBJECTIVE: The aim was to define characteristics measurable by three-dimensional imaging that would predict complexities both in the implantation procedure and the selection of the appropriate device size. METHODS: An anatomical study was performed of 50 postmortem hearts, of which 15 had a history of atrial fibrillation, and of 30 consecutive patients undergoing LAA occlusion with the Amplatzer cardiac plug (ACP). The specimens were classified according to variables that can be visualized using computerized tomography (CT). The CT scans of 30 consecutive patients were classified according to the level of the LAA ostium, the left lateral ridge (LLR), the LAA limbus and distance from LAA to the mitral annulus before undergoing LAA occlusion, and the results were correlated. RESULTS: Three types of LAA orifice were defined: type I, with a usually higher, anterior LAA ostium, a short, flattened and wide LLR and almost nonexistent limbus; type II, presenting a long, pointed and narrow LLR, and a longer, more defined limbus; type III, with a lower LAA ostium, close to the left atrium floor and the mitral annulus, a marked separation from the left pulmonary vein orifices and a limbus of intermediate length. CONCLUSION: LAA with lower ostia are more difficult to occlude. Types II and III have very prominent LLRs with longer limbi, which may increase the difficulty of inserting the guide and making measurements for selection of the right ACP size.

Resultados inmediatos y a más de un año en 35 pacientes consecutivos a los que se realiza cierre de orejuela izquierda con el dispositivo Amplatzer Cardiac Plug / Immediate and one-year results in 35 consecutive patients after closure of left atrial appendage with the amplatzer cardiac plug

Introducción y objetivos. El cierre del apéndice auricular izquierdo puede ser una opción terapéutica atractiva para pacientes con fibrilación auricular no valvular y contraindicación para tomar anticoagulantes orales, siempre que se obtengan buenos resultados durante la implantación y en el seguimiento. Métodos. Se analizó a 35 pacientes consecutivos y no elegibles para los estudios aleatorizados con anticoagulantes orales a los que se implantó el dispositivo oclusor Amplatzer. Tras los primeros 5 casos, se incorporó una técnica de imagen 3D. Se analizaron los resultados de la implantación y de seguimiento durante 1 año. Resultados. La media de edad era 74,65 ± 7,61 años, con un CHADS2 de 2,41 ± 1,53 y un CHA2DS2-VASc de 3,17 ± 1,60. No se pudo implantar el dispositivo en 1 caso y en 5 fue necesario cambiar la medida seleccionada. No hubo ninguna complicación cardiaca durante la implantación ni durante la estancia hospitalaria. Hubo una complicación vascular (fístula arteriovenosa). Se realizó seguimiento con ecocardiografía transesofágica a las 24 h y tras 1, 3, 6 y 12 meses; se documentaron 5 trombos, que se resolvieron con heparina. En el seguimiento de 21,14 ± 10,09 meses, hubo 3 muertes de pacientes mayores de 80 años, ninguna de ellas cardiológica, y un accidente isquémico transitorio sin secuelas. Conclusiones. El cierre del apéndice auricular izquierdo por un operador con cierta experiencia puede ser una opción terapéutica con pocas complicaciones y con resultados a más de 1 año eficaces en la reducción de complicaciones tromboembólicas y hemorrágicas, incluso en poblaciones de muy alto riesgo (AU)

Introduction and objectives. Left atrial appendage closure can be an attractive option for patients with nonvalvular atrial fibrillation and a contraindication to oral anticoagulants, provided that satisfactory results can be achieved during implantation and follow-up. Methods. Thirty-five consecutive patients, not eligible for randomized trials with oral anticoagulants, had an Amplatzer occlusion device implanted under general anesthesia. After the first 5 patients, 3-dimensional imaging was incorporated. The results of the implantation and the follow-up were analyzed over a 1-year period. Results. The mean age was 74.65 (7.61) years, with a CHADS2 score of 2.41 (1.53) and a CHA2DS2-VASc score of 3.17 (1.60). Implantation failed in 1 patient and 5 needed a change in the selected plug size. There were no cardiac complications during the implantation or hospital stay. There was 1 vascular complication (arteriovenous fistula). Transesophageal echocardiography monitoring was performed at 24h, 1, 3, 6, and 12 months and we found 5 thrombi which were resolved with heparin. In the follow-up period of 21.14 (10.09) months, 3 patients aged>80 years died, none of them due to heart problems, and one transient ischemic stroke without further consequences. Conclusions. Left atrial appendage closure by an experienced operator can be a treatment option with few complications and with efficient results at>1 year in reducing thromboembolic and hemorrhagic complications, even in very high-risk groups (AU)

Immediate and one-year results in 35 consecutive patients after closure of left atrial appendage with the Amplatzer cardiac plug.

INTRODUCTION AND OBJECTIVES: Left atrial appendage closure can be an attractive option for patients with nonvalvular atrial fibrillation and a contraindication to oral anticoagulants, provided that satisfactory results can be achieved during implantation and follow-up. METHODS: Thirty-five consecutive patients, not eligible for randomized trials with oral anticoagulants, had an Amplatzer occlusion device implanted under general anesthesia. After the first 5 patients, 3-dimensional imaging was incorporated. The results of the implantation and the follow-up were analyzed over a 1-year period. RESULTS: The mean age was 74.65 (7.61) years, with a CHADS2 score of 2.41 (1.53) and a CHA2DS2-VASc score of 3.17 (1.60). Implantation failed in 1 patient and 5 needed a change in the selected plug size. There were no cardiac complications during the implantation or hospital stay. There was 1 vascular complication (arteriovenous fistula). Transesophageal echocardiography monitoring was performed at 24h, 1, 3, 6, and 12 months and we found 5 thrombi which were resolved with heparin. In the follow-up period of 21.14 (10.09) months, 3 patients aged>80 years died, none of them due to heart problems, and one transient ischemic stroke without further consequences. CONCLUSIONS: Left atrial appendage closure by an experienced operator can be a treatment option with few complications and with efficient results at>1 year in reducing thromboembolic and hemorrhagic complications, even in very high-risk groups.