Mutations in TRIM63 cause an autosomal-recessive form of hypertrophic cardiomyopathy.

OBJECTIVE: Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. TRIM63 has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants in TRIM63 and the development of HCM. METHODS: TRIM63 was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls. RESULTS: Sixteen index cases with rare homozygous or compound heterozygous variants in TRIM63 (15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15-69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%). CONCLUSION: TRIM63 appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction.

Angiotomografía de las variantes anatómicas de la arteria cística: estudio en el preoperatorio de colelitiasis / Angiotomography of the anatomical variants of the cystic artery: pre-operative study of cholelithiasis

La colecistectomía laparoscópica es el tratamiento indicado en la colelitiasis, sin embargo el procedimiento no está exento de complicaciones o morbilidad concomitante. Es posible que, debido a lesiones ductales colaterales, ocurra sangrado con posibilidad de conversión de la cirugía e indeseables resultados. Para un correcto abordaje de la región se hace fundamental la identificación del trígono cistohepático (TCH) y sus componentes, a su vez de la ligadura y sección de la arteria cística (AC). Conociendo la elevada variabilidad de la AC, el objetivo de este trabajo consistió en identificar el número, origen, trayecto y relación de la AC con el TCH y sus variaciones, utilizando angiotomografía por medio de un tomógrafo detector de 64 cortes, en el preoperatorio de 30 pacientes de sexo femenino, entre 24 y 54 años de edad, con colelitiasis diagnosticadas clínicamente y por ecosonografía. La AC en el 76,67 % era única y se encontraba dentro del TCH, en el 16,67 % era única y se observó fuera del TCH. En el 6,67 % se observaron dos AC, una dentro y otra fuera del TCH. En el 66,67 % de los casos la AC se originaba de manera normal de la arteria hepática derecha. La trazabilidad de la AC fue en el 53,3 % medianamente visible y en el 46,7 % de trazabilidad excelente. En conclusión, la identificación de la AC y sus variaciones anatómicas se puede determinar en el preoperatorio y puede ser útil para mejorar el plan quirúrgico en pacientes con colelitiasis, brindando información al procedimiento, optimizarlo y disminuir los riesgos de eventuales complicaciones relacionados con sangrado.

Laparoscopic cholecystectomy is the treatment indicated for cholelithiasis, however the procedure is not free of complications or concomitant morbidity. It is possible that, due to collateral ductal lesions, bleeding occurs with the possibility of surgery conversion and undesirable results. For a correct approach to the region it is essential to identify the cystohepatic trigone (CHT) and its components, as well as the ligation and section of the cystic artery (AC). Knowing the high variability of CA, the aim of this work was to identify the number, origin, path and relationship of CA with the CHT and its variations using angiotomography by means of a 64-slice detector tomograph in the preoperative period of 30 female patients, between 24 and 54 years old, with clinically diagnosed cholelithiasis and by echo sonography. The AC in 76.67 % was unique and was within the CHT, in 16.67 % it was unique and was observed outside the CHT. In 6.67 %, two ACs were observed, one inside and one outside the TCH. In 66.67 % of cases, CA originated normally from the right hepatic artery. The traceability of AC was 53.3 % moderately visible and 46.7 % excellent traceability. In conclusion, the identification of AC and its anatomical variations can be determined in the preoperative period and can be useful to improve the surgical plan in patients with cholelithiasis, providing information on the procedure, optimizing it and reducing the risks of possible bleeding related complications.

Fibroblast growth factor-23 promotes rhythm alterations and contractile dysfunction in adult ventricular cardiomyocytes.

BACKGROUND: Cardiac dysfunction and arrhythmia are common and onerous cardiovascular events in end-stage renal disease (ESRD) patients, especially those on dialysis. Fibroblast growth factor (FGF)-23 is a phosphate-regulating hormone whose levels dramatically increase as renal function declines. Beyond its role in phosphorus homeostasis, FGF-23 may elicit a direct effect on the heart. Whether FGF-23 modulates ventricular cardiac rhythm is unknown, prompting us to study its role on excitation-contraction (EC) coupling. METHODS: We examined FGF-23 in vitro actions on EC coupling in adult rat native ventricular cardiomyocytes using patch clamp and confocal microscopy and in vivo actions on cardiac rhythm using electrocardiogram. RESULTS: Compared with vehicle treatment, FGF-23 induced a significant decrease in rat cardiomyocyte contraction, L-type Ca2+ current, systolic Ca2+ transients and sarcoplasmic reticulum (SR) load and SR Ca2+-adenosine triphosphatase 2a pump activity. FGF-23 induced pro-arrhythmogenic activity in vitro and in vivo as automatic cardiomyocyte extracontractions and premature ventricular contractions. Diastolic spontaneous Ca2+ leak (sparks and waves) was significantly increased by FGF-23 via the calmodulin kinase type II (CaMKII)-dependent pathway related to hyperphosphorylation of ryanodine receptors at the CaMKII site Ser2814. Both contraction dysfunction and spontaneous pro-arrhythmic Ca2+ events induced by FGF-23 were blocked by soluble Klotho (sKlotho). CONCLUSIONS: Our results show that FGF-23 reduces contractility and enhances arrhythmogenicity through intracellular Ca2+ mishandling. Blocking its actions on the heart by improving sKlotho bioavailability may enhance cardiac function and reduce arrhythmic events frequently observed in ESRD.

Mechanistic insights of the left ventricle structure and fibrosis in the arrhythmogenic mitral valve prolapse.

Mitral valve prolapse (MVP) is a common and benign condition. However, some anatomic forms have been recently associated with life-threatening ventricular arrhythmias and sudden cardiac death. Imaging MVP holds the promise of individualized MVP risk assessment. Noninvasive imaging techniques available today are playing an increasingly important role in the diagnosis, prognosis and monitoring of MVP. In this article, we will review the current evidence on arrhythmogenic MVP, with special focus on the utility of echocardiography and CMR for identifying benign and "malignant" forms of MVP. The clinical relevance of this manuscript lies in the value of imaging technology to improve MVP risk prediction, including those arrhythmic-MVP cases with a higher risk of sudden cardiac death.

Super-response to cardiac resynchronization therapy may predict late phrenic nerve stimulation.

Aims: Changes in the anatomical relationship between left phrenic nerve and coronary veins may occur due to the reverse remodelling observed in super-responders to cardiac resynchronization therapy (CRT) and might be the underlying mechanism in patients developing late-onset phrenic nerve stimulation (PNS) without evidence of lead dislodgement (LD). In this study, we sought to evaluate the role of super-response (SR) to CRT as a potential predictor of late-onset PNS. Methods and results: Consecutive patients implanted with a left ventricular (LV) lead in a single centre were retrospectively analysed. Phrenic nerve stimulation was classified as 'early' when it occurred within 3 months of implantation and 'late' for occurrences thereafter. 'Late' PNS was considered related to LD (LD-PNS) when LV threshold differed by > 1 V or impedance >250 Ω from baseline values or in case of radiological displacement. Cases not meeting the former criteria were classified as 'non-LD-PNS'. Super-response was defined as a decrease ≥30% of the left ventricluar end-systolic volume at 1-year echocardiography. At 32 ± 7 months follow-up, PNS occurred in 20 of 139 patients. Late non-LD-PNS incidence was significantly higher in the SR group (8/61; 13.1%) when compared with the non-SR (1/78; 1.3%) (P = 0.010). Super-response remained the only predictor of non-LD-PNS at multivariate analysis (odds ratio: 11.62, 95% confidence interval 1.41-95.68, P = 0.023). Conclusion: Incidence of late non-LD-PNS is higher among SR to CRT, suggesting a potential role of the changes in the anatomical relationship between left phrenic nerve and coronary veins.

Estimulación frénica de aparición tardía en paciente superrespondedor a la terapia de resincronización. ¿El precio del éxito? / Late phrenic nerve stimulation in a super-responder to cardiac resynchronization therapy. The toll of success?

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Atrial Rate-Responsive Pacing and Incidence of Sustained Atrial Arrhythmias in Patients with Implantable Cardioverter Defibrillators.

BACKGROUND: Atrial rate-responsive pacing (RRP) has proved to be safe in pacemaker recipients with chronotropic incompetence. Although RRP is available in all current implantable cardioverter defibrillators (ICDs), the outcomes of this pacing mode in ICD patients are unknown. The aim is to evaluate the relationship between atrial RRP and atrial arrhythmias in ICD recipients. METHODS: Dual-chamber and triple-chamber ICD patients were included in this multicenter cohort study. Patients with permanent atrial fibrillation (AF) or VVI pacing mode were excluded. The number and duration of atrial tachycardia (AT)/AF episodes were assessed. RESULTS: Data from 415 patients and 80,707 AT/AF episodes (median duration: 0.4 hours) were collected after a 21.3 ± 14.1-month follow-up. Atrial RRP was programmed in 90 (21.7%) patients and was associated with a higher atrial pacing percentage in the overall study population (51.2 ± 33.8% vs 18.4 ± 25.7%, P < 0.001) and to a higher ventricular pacing percentage among dual-chamber devices (22.3 ± 37.6% vs 9.3 ± 25%, P < 0.001). Independent factors associated with sustained AT/AF episodes (>23 hours) were previous AF (odds ratio [OR]: 7.98; 95% confidence interval [CI]: 4.11-15.47; P < 0.001) and atrial RRP (OR: 3.58; 95% CI: 1.82-7.03; P < 0.001). RRP was related to a lower sustained AT/AF episodes-free survival both in patients with a history of AF (43% vs 70%, P = 0.035) and without a history of AF (82% vs 97%, P = 0.004) at 2 years. CONCLUSIONS: Atrial RRP in ICD patients was related to a higher incidence of sustained atrial arrhythmias. This pacing mode may have an atrial proarrhythmic effect on ICD patients, especially among those with a history of AF.

Cavo-tricuspid isthmus radiofrequency ablation using a novel remote navigation catheter system in patients with typical atrial flutter.

AIMS: A new remote catheter system (AMIGO™ Remote Catheter System) compatible with conventional ablation catheters is now commercially available but no data about its performance in clinical use during ablation have been reported. This study evaluates the feasibility, efficacy, and safety of cavo-tricuspid isthmus (CTI) ablation with this system in patients with typical atrial flutter (AFl). METHODS AND RESULTS: Sixty patients with typical AFl underwent CTI ablation using the new remote catheter navigation system with 8 mm tip or irrigated catheters in three centres following each centre's routine practice. The endpoint was stable bidirectional CTI block. CTI ablation was successful in 98% of patients. Ablation was completed manually in one patient. The overall procedure, fluoroscopy, and radiofrequency times (median ± standard deviation, range) were 123 ± 42 (50-250), 24 ± 13 (3-82), and 10 ± 8 (1.17-43.3) min, respectively. Three patients had vascular complications not requiring surgical intervention. There were no complications related to the remote catheter manipulation system. CONCLUSION: Cavo-tricuspid isthmus ablation for typical AFl can be safely and effectively performed with the AMIGO™. The learning curve seems to be short even for physicians with limited ablation experience.

Congenital complete atrioventricular block associated with QT prolongation: Description of a patient with an unusual outcome.

The association of a complete atrioventricular block with long QT syndrome is relatively common and carries a high risk of torsades de pointes (TdP) and sudden death. It is probably due to a downregulation of potassium channel currents (I (Ks) and I (Kr)) that impairs ventricular repolarization, prolongs the QT interval and increases susceptibility to TdP, so it must be considered a channelopathy. This report describes a 6 year-old boy, with a complete atrioventricular block diagnosed at 5 months of age, who at the age of 1 year started having episodes of TdP associated with a prolonged QT interval. He was treated successfully with propranolol and with a pacemaker implant. At age 3 the complete atrioventricular block reversed spontaneously to a first degree atrioventricular block.

Algunos aspectos relacionados con la implantación del desfibrilador automático implantable / Factors associated with the implantation of implantable cardioverter–defibrillators

Tras demostrar la eficacia del desfibrilador automático implantable para reducir la mortalidad en ciertos grupos de pacientes, esencialmente con los sistemas monocamerales, se discuten las ventajas y limitaciones de los sistemas bicamerales en diferentes situaciones. Asimismo, se plantean las crecientes indicaciones de los sistemas con terapia de resincronización añadida. Asegurar la eficacia de la desfibrilación de un dispositivo ha sido objeto de diferentes estudios y uno de los pilares durante el implante. Sin embargo, la metodología empleada para su determinación ha sido variable, ha evolucionado y hasta ha llegado a cuestionarse su comprobación. Uno de los elementos importantes que ha de tenerse en cuenta en el momento del implante es la aparición de complicaciones, tanto de forma inmediata como a largo plazo. Se resume y analiza la abundante bibliografía al respecto, recalcándose su incidencia y su posible prevención. Estos aspectos resultan esenciales para reducir la morbilidad relacionada con el implante (AU)

The effectiveness of implantable cardioverter-defibrillators in reducing mortality in some groups of patients has been primarily demonstrated with single-chamber devices. Here, the advantages and limitations of dual-chamber devices in various situations are discussed. In addition, the growing number of indications for systems with concomitant resynchronization therapy is also considered. Defibrillation efficacy testing has been the focus of numerous studies and is a main consideration during implantation. However, the methodology used for such tests has changed and evolved over the years, to the point that its validity has been questioned. One important factor that must be taken into account during implantation is the development of complications that may have short- or long-term consequences. The extensive literature on this topic is summarized and reviewed, with an emphasis on the incidence of complications and their prevention. These considerations are essential for reducing morbidity associated with device implantation (AU)

Pulmonary arterial hypertension: noninvasive detection with phase-contrast MR imaging.

PURPOSE: To retrospectively identify pulmonary arterial (PA) flow parameters measured with phase-contrast magnetic resonance (MR) imaging that allow noninvasive diagnosis of chronic PA hypertension (PAH). MATERIALS AND METHODS: The study was HIPAA compliant and was approved by the institutional review board; a waiver of informed consent was obtained. Fifty-nine patients (49 female patients; mean age, 46 years; range, 16-85 years) known to have or suspected of having PAH underwent breath-hold phase-contrast MR imaging and right-sided heart catheterization (RHC). The presence of PAH (mean pulmonary artery pressure [mPAP], >25 mm Hg) was confirmed in 42 patients. Parameters, including PA areas, PA strain, average velocity, peak velocity, acceleration time, and ejection time, were measured in each patient by investigators blinded to RHC results. These measurements were correlated with mPAP, systolic pulmonary artery pressure (sPAP), and pulmonary vascular resistance index (PVRI). The diagnostic ability of phase-contrast MR imaging to depict PAH was quantified. Statistical tests included Spearman rho coefficients, receiver operating characteristic curve analysis, and Bland-Altman plots. RESULTS: Results showed average velocity to have the best correlation with mPAP, sPAP, and PVRI (r = -0.73, -0.76, and -0.86, respectively; P < .001). Average velocity (cutoff value = 11.7 cm/sec) revealed PAH with a sensitivity of 92.9% (39 of 42) and a specificity of 82.4% (14 of 17). Sensitivity and specificity for the minimum PA area (cutoff value = 6.6 cm(2)) were 92.9% (39 of 42) and 88.2% (15 of 17), respectively. CONCLUSION: The average blood velocity throughout the cardiac cycle is strongly correlated with pulmonary pressures and resistance.

Análisis descriptivo del hueso astrágalo o talus / Descriptive analysis of astragalus bone or talus

Tipo de estudio: descriptivo-analítico.Objetivo: estudiar las características morfológicas del hueso astrágalo, considerando sus depresiones leves y profundas, así como las superficies salientes y articulares para elaborar una descripción propia.Método: se observaron y analizaron 20 huesos tomados de distintos cadáveres adultos. Se midieron todas las características encontradas del hueso y las descritas por la bibliografía actual.Resultados: se observaron y midieron 17 características que se tabularon y promediaron; por ejemplo la prolongación de 5.9mm de la apófisis externa y la polea astragalina que presentó una extensión anteroposterior promedio de 3,75cm y el diámetro transversal promedio de 2,8cm; estos detalles y otros permitieron elaborar una descripción propia e inédita.Conclusiones: el estudio del hueso permitió establecer características morfológicas diferentes con relación a las descripciones clásicas lo que demuestra que la morfología de la muestra estudiada presenta diferencias debido a las características socioculturales del medio. La elaboración de esta descripción sin antecedentes en nuestra literatura, servirá de ayuda para anatomistas, radiólogos, traumatólogos, rehabilitadores y deportólogos para el manejo de lesiones y de las articulaciones que la rodean. Se concluye que existen diferencias con la descripción clásica producto de la morfología autóctona.

Descriptive-analytical study Objective: To study the morphologic traits of the astragalus bone considering its superficial and deep depressions as well as the articular structures to elaborate a proper description.Method: Twenty bones were collected from different adult cadavers and were studied to describe the characteristics found. Results: Seventeen different structural characteristics were measured to elaborate a proper description. For example: the length of the external apophysis and a pulley like structure with anteroposterior extension of 3.75cm and the cross-sectional diameter an average of 2.8cm.Conclusions: the study of the bone allowed to establish different morphologic characteristics in relation to the classic descriptions. This demonstrates that the differences are due to the socio-cultural environmental characteristics. The elaboration of this description, will serve to support anatomists, radiologist, traumatologist, physiotherapist and sport physicians for the handling of its injury and to structures that surrounds it.

Bloqueo auriculoventricular completo transitorio tras traumatismo torácico cerrado / Transient Complete Atrioventricular Block Following a Nonpenetrating Chest Trauma

La contusión miocárdica puede ocasionar trastornos en la formación y en la propagación de los impulsos eléctricos en el sistema específico de conducción. La aparición de un bloqueo auriculoventricular completo transitorio tras un traumatismo torácico cerrado es una complicación poco frecuente. Se describe el caso de un paciente que tras sufrir un traumatismo torácico cerrado debido a un accidente de tráfico presentó, de manera transitoria, un bloqueo auriculoventricular completo y posteriormente un bloqueo de rama derecha con hemibloqueo anterior izquierdo. Se resalta la dificultad para el diagnóstico de contusión miocárdica y se discute la utilidad del estudio electrofisiológico para descartar la existencia de alteraciones basales del sistema específico de conducción (AU)