Myocardial fibrosis in arrhythmogenic cardiomyopathy: a genotype-phenotype correlation study.

AIMS: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a life-threatening entity with a highly heterogeneous genetic background. Cardiac magnetic resonance (CMR) imaging can identify fibrofatty scar by late gadolinium enhancement (LGE). Our aim is to investigate genotype-phenotype correlation in ARVC/D mutation carriers, focusing on CMR-LGE and myocardial fibrosis patterns. METHODS AND RESULTS: A cohort of 44 genotyped patients, 33 with definite and 11 with borderline ARVC/D diagnosis, was characterized using CMR and divided into groups according to their genetic condition (desmosomal, non-desmosomal mutation, or negative). We collected information on cardiac volumes and function, as well as LGE pattern and extension. In addition, available ventricular myocardium samples from patients with pathogenic gene mutations were histopathologically analysed. Half of the patients were women, with a mean age of 41.6 ± 17.5 years. Next-generation sequencing identified a potential pathogenic mutation in 71.4% of the probands. The phenotype varied according to genetic status, with non-desmosomal male patients showing lower left ventricular (LV) systolic function. LV fibrosis was similar between groups, but distribution in non-desmosomal patients was frequently located at the posterolateral LV wall; a characteristic LV subepicardial circumferential LGE pattern was significantly associated with ARVC/D caused by desmin mutation. Histological analysis showed increased fibrillar connective tissue and intercellular space in all the samples. CONCLUSION: Desmosomal and non-desmosomal mutation carriers showed different morphofunctional features but similar LV LGE presence. DES mutation carriers can be identified by a specific and extensive LV subepicardial circumferential LGE pattern. Further studies should investigate the specificity of LGE in ARVC/D.

Diagnosis, management and mortality in acute aortic syndrome: results of the Spanish Registry of Acute Aortic Syndrome (RESA-II).

BACKGROUND: Recent advances in the diagnosis and treatment of acute aortic syndrome should improve the outcome of this disease. The Spanish Registry of Acute Aortic Syndrome aimed to assess current results in acute aortic syndrome management in a wide cohort of hospitals in the same geographical area. METHODS: From January 2012 to January 2014, 26 tertiary hospitals included 629 consecutive patients with acute aortic syndrome: 73% men, mean age 64.7±14 years (range 22-92), 443 type A (70.4%) and 186 type B (29.6%). RESULTS: Time elapsed between symptom onset and diagnosis was <12 hours in 70.7% of cases and <24 hours in 84.0% (median 5 hours; 25th-75th percentiles, 2.7-15.5 hours). Computed tomography was the first diagnostic technique in 78% of patients and transthoracic echocardiography in 15%. Surgical treatment was indicated in 78.3% of type A acute aortic syndrome. The interval between diagnosis and surgery was 4.8 hours (quartile 1-3, 2.5-11.4 hours). Among the patients with type B acute aortic syndrome, treatment was medical in 116 cases (62.4%), endovascular in 61 (32.8%) and surgical in nine (4.8%). Type A mortality during hospitalisation was 25.1% in patients treated surgically and 68% in those treated medically. Mortality in type B was 13.8% in those with medical treatment, 18.0% with endovascular therapy and 33.0% with surgical treatment. CONCLUSION: Improvements in the diagnosis and treatment of acute aortic syndrome have not resulted in a significant reduction in hospital mortality. The results of this study reflect more overall and less selected information on acute aortic syndrome management and the need for sustained advances in the therapeutic strategy of acute aortic syndrome.

Diagnóstico clínico y genético de la muerte súbita cardiaca de origen no isquémico / Clinical and genetic diagnosis of nonischemic sudden cardiac death

Introducción y objetivos: La muerte súbita cardiaca (MSC) de origen no isquémico está causada predominantemente por miocardiopatías y canalopatías. La batería de test diagnósticos es amplia e incluye pruebas complejas. El objetivo de nuestro estudio es analizar la rentabilidad diagnóstica del estudio etiológico sistematizado de la MSC. Métodos: Se estudió a 56 familias con al menos 1 caso índice con MSC (reanimada o no). En los supervivientes se exploró con electrocardiograma, imagen cardiaca avanzada, ergometría, estudio familiar, estudio genético y, puntualmente, test farmacológicos. En los fallecidos se examinó la necropsia, así como la autopsia molecular con next generation sequencing (NGS), junto con estudio clínico familiar. Resultados: El diagnóstico se alcanzó en el 80,4% de los casos, sin diferencias entre supervivientes y fallecidos (p = 0,53). Entre los supervivientes, el diagnóstico de canalopatía fue más frecuente que entre los fallecidos (el 66,6 frente al 40%; p = 0,03). De los 30 sujetos fallecidos, en 7 la autopsia aportó un hallazgo concluyente. El diagnóstico de miocardiopatía tendía a asociarse con mayor tasa de eventos en la familia. El test genético con NGS se realizó en 42 de los casos; se obtuvo resultado positivo en 28 (66,6%), sin diferencias entre supervivientes y fallecidos (p = 0,21). Conclusiones: La probabilidad de alcanzar el diagnóstico en la MSC tras un protocolo exhaustivo es alta, con mayor prevalencia de canalopatías en los supervivientes y un aparente peor pronóstico en las miocardiopatías. El test genético mediante NGS muestra utilidad en casos de MSC e incrementa la rentabilidad respecto al estudio con Sanger (AU)

Introduction and objectives: Nonischemic sudden cardiac death (SCD) is predominantly caused by cardiomyopathies and channelopathies. There are many diagnostic tests, including some complex techniques. Our aim was to analyze the diagnostic yield of a systematic diagnostic protocol in a specialized unit. Methods: The study included 56 families with at least 1 index case of SCD (resuscitated or not). Survivors were studied with electrocardiogram, advanced cardiac imaging, exercise testing, familial study, genetic testing and, in some cases, pharmacological testing. Families with deceased probands were studied using the postmortem findings, familial evaluation, and molecular autopsy with next-generation sequencing (NGS). Results: A positive diagnosis was obtained in 80.4% of the cases, with no differences between survivors and nonsurvivors (P = .53). Cardiac channelopathies were more prevalent among survivors than nonsurvivors (66.6% vs 40%, P = .03). Among the 30 deceased probands, the definitive diagnosis was given by autopsy in 7. A diagnosis of cardiomyopathy tended to be associated with a higher event rate in the family. Genetic testing with NGS was performed in 42 index cases, with a positive result in 28 (66.6%), with no differences between survivors and nonsurvivors (P = .21). Conclusions: There is a strong likelihood of reaching a diagnosis in SCD after a rigorous protocol, with a more prevalent diagnosis of channelopathy among survivors and a worse familial prognosis in cardiomyopathies. Genetic testing with NGS is useful and its value is increasing with respect to the Sanger method (AU)

Clinical and Genetic Diagnosis of Nonischemic Sudden Cardiac Death.

INTRODUCTION AND OBJECTIVES: Nonischemic sudden cardiac death (SCD) is predominantly caused by cardiomyopathies and channelopathies. There are many diagnostic tests, including some complex techniques. Our aim was to analyze the diagnostic yield of a systematic diagnostic protocol in a specialized unit. METHODS: The study included 56 families with at least 1 index case of SCD (resuscitated or not). Survivors were studied with electrocardiogram, advanced cardiac imaging, exercise testing, familial study, genetic testing and, in some cases, pharmacological testing. Families with deceased probands were studied using the postmortem findings, familial evaluation, and molecular autopsy with next-generation sequencing (NGS). RESULTS: A positive diagnosis was obtained in 80.4% of the cases, with no differences between survivors and nonsurvivors (P=.53). Cardiac channelopathies were more prevalent among survivors than nonsurvivors (66.6% vs 40%, P=.03). Among the 30 deceased probands, the definitive diagnosis was given by autopsy in 7. A diagnosis of cardiomyopathy tended to be associated with a higher event rate in the family. Genetic testing with NGS was performed in 42 index cases, with a positive result in 28 (66.6%), with no differences between survivors and nonsurvivors (P=.21). CONCLUSIONS: There is a strong likelihood of reaching a diagnosis in SCD after a rigorous protocol, with a more prevalent diagnosis of channelopathy among survivors and a worse familial prognosis in cardiomyopathies. Genetic testing with NGS is useful and its value is increasing with respect to the Sanger method.

Herencia autosómica recesiva como causa de miocardiopatía arritmogénica biventricular / A Recessive Inheritance Pattern Contributes to Arrhythmogenic Biventricular Cardiomyopathy

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[Left ventricular dysfunction induced by monomorphic ventricular arrhythmias: large improvement in ventricular function after radiofrequency ablation of the arrhythmic source]. / Disfunción ventricular izquierda inducida por arritmias ventriculares monomórficas: gran mejoría de la función ventricular tras ablación con radiofrecuencia del foco arrítmico.

Left ventricular systolic dysfunction related to ventricular arrhythmias is a relatively poorly understood entity. To increase our knowledge base, we describe 5 patients in whom the link between ventricular dysfunction and ventricular arrhythmia was unequivocally established. All patients had repetitive monomorphic ventricular arrhythmias and left ventricular systolic dysfunction (ejection fraction < or =40% and end-diastolic size > or =55 mm). The arrhythmogenic source was identified by electrophysiological study (right ventricle in 2 patients, left ventricle in 2, and left sinus of Valsalva in one), and was eliminated in all patients by radiofrequency catheter ablation. At 7+/-2 months post-ablation, large improvements were seen in left ventricular function and remodeling (ejection fraction >/=50% and end-diastolic size < or =51 mm in all cases), with no recurrence of arrhythmia during follow-up (10-69 months). This finding confirms that recurring ventricular arrhythmias can induce left ventricular dysfunction which may be reversible after ablation.

Disfuncion ventricular izquierda inducida por arritmias ventriculares monomorficas: gran mejoria de la funcion ventricular tras ablacion con radiofrecuencia del foco arritmico / Left ventricular dysfunction induced by monomorphic ventricular arrhythmias: large improvement in ventricular function after radiofrequency ablation of the arrhythmic source

Disfunción ventricular izquierda inducida por arritmias ventriculares monomórficas: gran mejoría de la función ventricular tras ablación con radiofrecuencia del foco arrítmico. La disfunción ventricular izquierda ocasionada por arritmias ventriculares es una entidad poco conocida. Para contribuir a su difusión presentamos los casos de 5 pacientes en los que se pudo establecer de forma inequívoca la conexión arritmia-disfunción ventricular. Todos tenían arritmias ventriculares monomórficas repetitivas y disfunción ventricular izquierda(fracción de eyección ? 40% y dimensión tele-diastólica ? 55 mm). En el estudio electrofisiológico se detectó un foco arritmogénico intraventricular localizado en el ventrículo derecho en 2 casos, en el ventrículo izquierdo en otros 2 y en el seno de Valsalva izquierdo en el quinto; en todos fue suprimido mediante ablación con catéter. A los 7 ± 2 meses postablación se observó una gran mejoría de la función sistólica y el remodelado ventricular izquierdo (fracción de eyección ? 50% y dimensión telediastólica ? 51 mm en los 5 enfermos), sin recurrencia de la arritmia durante el seguimiento(10-69 meses). Estos hallazgos confirman que las arritmias ventriculares repetitivas pueden causar disfunción ventricular, reversible tras ablación con radiofrecuencia

Left ventricular systolic dysfunction related to ventricular arrhythmias isa relatively poorly understood entity. To increase our knowledge base, we describe 5 patients in whom the link between ventricular dysfunction and ventricular arrhythmia was unequivocally established. All patients had repetitive monomorphic ventricular arrhythmias and left ventricular systolicdys function (ejection fraction ?40% and end-diastolic size ?55 mm). The arrhythmogenic source was identified by electrophysiological study (right ventricle in 2 patients, left ventricle in 2, and left sinus of Valsalva inone), and was eliminated in all patients by radiofrequency catheter ablation. At 7±2 months post-ablation, large improvements were seen in left ventricular function and remodeling (ejection fraction ?50% and end-diastolic size ?51 mm in all cases), with no recurrence of arrhythmia during follow-up (10-69 months). This finding confirms that recurring ventricular arrhythmias can induce left ventricular dysfunction which may be reversible after ablation

Utility of adenosine 5'-triphosphate in predicting early recurrence after successful ablation of manifest accessory pathways.

OBJECTIVES: The purpose of this study was to determine whether administration of adenosine 5'-triphosphate (ATP; 20-40 mg) after successful ablation of accessory pathway (AP) with manifest preexcitation is useful for detecting residual conduction and predicting early recurrences. BACKGROUND: The reported incidence of recurrence of AP conduction after an initially successful procedure is 5% to 10%. Little information on the variables related to early recurrence has been reported. METHODS: We prospectively used 108 ATP tests on 100 consecutive patients (66 men, mean age 36 +/- 15 years) with manifest preexcitation. Five minutes after successful ablation, intravenous boluses of ATP at increasing doses were injected until the target effect of second- or third-degree AV block or AP conduction was observed. RESULTS: The effect of ATP was AV block (negative test) in 82 cases (76%), conduction over previously ablated AP (positive test) in 9 cases (8.3%), and no achievement of target effect (nondiagnostic test) in 17 cases (15.7%). Thirteen early recurrences were observed in 12 patients. In all 9 (100%) patients with positive ATP test and in 4 (4.9%) of the 82 patients with negative ATP test, conduction over the AP recurred (relative risk 20; 95% confidence interval 8-53; P < .000001). The diagnostic accuracy of the test (analyzing the target effect) was 95%, sensitivity 69%, specificity 100%, and positive and negative predictive values 100% and 95%, respectively. CONCLUSIONS: ATP administration after successful ablation of APs has a high predictive value for early recurrence and may help optimize the duration of the ablation procedure.

Fibroelastoma papilar cardíaco: una causa tratable de accidente cerebrovascular / Cardiac papillary fibroelastoma: a treatable cause of cerebrovascular events

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[Does the EuroSCORE identify patients at minimum risk of mortality from heart surgery?]. / ¿Se puede identificar mediante el EuroSCORE a los pacientes con mortalidad mínima en cirugía cardíaca?

INTRODUCTION AND OBJECTIVES: Risk of hospital death is one of the key factors considered by the clinical cardiologist when weighting indications for surgery. Risk estimation scales establish distinct levels of risk in quantitative terms. The aim of the present study was to investigate whether a low EuroSCORE value corresponds to low mortality in our setting. PATIENTS AND METHODS: During 1999-2000 we prospectively calculated the EuroSCORE for all patients who underwent isolated coronary (CS) or valvular (VS) surgery. We then analyzed intrahospital mortality of patients with a low EuroSCORE. The validation group consisted of patients who underwent surgery in 2001 and obtained a low EuroSCORE. RESULTS: During 1999-2000 we identified 116 patients (16.2% of all patients treated with isolated CS or CV) with a low EuroSCORE (50 8.6 years; 65% male). Fifty-seven of these patients underwent isolated CS, and 59 of them isolated VS. Intrahospital mortality was zero. In 2001 we identified 59 (16.1%) such patients (49 8.7 years; 68% male), of whom 35 underwent isolated CS and 24 underwent isolated VS. Intrahospital mortality during this period was again zero. CONCLUSIONS: A low EuroSCORE identifies a population of patients with minimum risk of mortality after isolated coronary or valve surgery. The score may be useful as a sentinel indicator in analyses of the complex issue of quality of cardiac surgery.

¿Se puede identificar mediante el EuroSCORE a los pacientes con mortalidad mínima en cirugía cardíaca? / Does the EuroSCORE identify patients at minimum risk of mortality from heart surgery?

Introducción y objetivos. El nivel de riesgo de muerte hospitalaria ha sido uno de los factores clave que el cardiólogo clínico ha sopesado a la hora de establecer una indicación quirúrgica. Las escalas de estimación de riesgo evalúan cuantitativamente el riesgo, estableciendo niveles muy diferentes. El objetivo de nuestro estudio es investigar si, en nuestro medio, un valor mínimo del EuroSCORE se corresponde, en efecto, con una mínima mortalidad. Pacientes y métodos. Durante 1999 y 2000 cuantificamos prospectivamente el EuroSCORE de todos los pacientes con cirugía de revascularización coronaria y valvular aisladas. Analizamos la mortalidad intrahospitalaria en aquellos con un valor mínimo del EuroSCORE. Los pacientes intervenidos en el año 2001 que obtuvieron un valor mínimo del EuroSCORE constituyeron el grupo de validación. Resultados. Durante 1999-2000 identificamos a 116 (16,2 por ciento del total de la cirugía de revascularización coronaria y cirugía valvular aisladas) pacientes (50 ñ 8,6 años; un 65 por ciento, varones) con un valor mínimo del EuroSCORE. Se realizó cirugía coronaria en 57 pacientes y cirugía valvular en 59. La mortalidad intrahospitalaria fue nula. En el año 2001 identificamos a 59 (16,1 por ciento del total) pacientes (un 68 por ciento, varones; 49 ñ 8,7 años). De ellos, 35 fueron sometidos a cirugía coronaria y 24 a cirugía valvular. La mortalidad en este período también fue nula. Conclusiones. Un valor mínimo del EuroSCORE identifica a una población de pacientes cuyo riesgo de fallecimiento, tras una cirugía coronaria o valvular aisladas, es mínimo. Este valor podría ser utilizado como indicador centinela en el complejo tema de la calidad en la cirugía cardíaca (AU)