Index and Repeat Ablation for Atrial Fibrillation in Older versus Younger Patients: A Propensity-Score Matching Analysis.

Catheter ablation is a well-established rhythm control therapy in atrial fibrillation (AF). Although the prevalence of AF increases dramatically with age, the prognosis and safety profile of index and repeat ablation procedures remain unclear in the older population. The primary endpoint of this study was to assess the arrhythmia recurrence, reablation and complication rates in older patients. Secondary endpoints were the identification of independent predictors of arrhythmia recurrence and reablation, including information on pulmonary vein (PV) reconnection and other atrial foci. Older (n=129, ≥70 years) and younger (n=129, <70 years) patients were compared using a propensity-score matching analysis based on age, gender, obesity, hypertension, dyslipidemia, diabetes mellitus, dilated left atrium, severe obstructive sleep apnea, cardiac disease, left systolic ventricular function, AF pattern and ablation technique. Arrhythmia recurrence and reablation were evaluated in both groups using a Cox regression analysis in order to identify predictors. During a 30-month follow-up period, there were no significant differences between older and younger patients in the arrhythmia-free survival (65.1% and 59.7%; log-rank test p=0.403) and complication (10.1% and 10.9%; p>0.999) rates after the index ablation. However, the reablation rate was significantly different (46.7% and 69.2%; p<0.05, respectively). In those patients who underwent reablation procedure (redo subgroups), there were no differences in the incidence of PV reconnection (38.1% redo-older and 27.8% redo-younger patients; p=0.556). However, the redo-older patients had lower reconnected PVs per patient (p<0.01) and lower atrial foci (2.3 and 3.7; p<0.01) than the redo-younger patients. A further important finding was that age was not an independent predictor of arrhythmia recurrence or reablation. Our data reveal that the AF index ablation in older patients had a similar efficacy and safety profile to younger patients. Therefore, age alone must not be considered a prognostic factor for AF ablation but the presence of limiting factors such as frailty and multiple comorbidities.

The Novel Variant NP_00454563.2 (p.Glu259Glyfs*77) in Gene PKP2 Associated with Arrhythmogenic Cardiomyopathy in 8 Families from Malaga, Spain.

INTRODUCTION AND OBJECTIVES: Arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease defined by the progressive replacement of the ventricular myocardium with fibroadipose tissue, which can act as a substrate for arrhythmias, sudden death, or even give rise to heart failure (HF). Sudden death is frequently the first manifestation of the disease, particularly among young patients. The aim of this study is to describe a new pathogenic variant in the PKP2 gene. METHODS: A descriptive observational study that included eight initially non-interrelated families with a diagnosis of ACM undergoing follow-up at our HF and Familial Cardiomyopathies Unit, who were carriers of the NM_004572.3:c.775_776insG; p.(Glu259Glyfs*77) variant in the PKP2 gene. The genetic testing employed next-generation sequencing for the index cases and the Sanger method for the targeted study with family members. We compiled personal and family histories, demographic and clinical characteristics, data from the additional tests at the time of diagnosis, and arrhythmic events at diagnosis and during follow-up. RESULTS: We included 47 subjects, of whom 8 were index cases (17%). Among the evaluated family members, 16 (34%) were carriers of the genetic variant, 3 of whom also had a diagnosis of ACM. The majority were women (26 patients; 55.3%), with a mean age on diagnosis of 48.9 ± 18.6 years and a median follow-up of 39 [24-59] months. Worthy of note are the high incidences of arrhythmic events as the form of presentation and in follow-up (21.5% and 20.9%, respectively), and the onset of HF in 25% of the sample. The most frequent ventricular involvements were right (four patients, 16.7%) and biventricular (four patients, 16.7%); we found no statistical differences in any of the variables analysed. CONCLUSIONS: This variant is a pathogenic variant of gene PKP2 that has not previously been described and is not present in the control groups associated with ACM. It has incomplete penetrance, a highly variable phenotypic expressivity, and was identified in eight families of our geographical area in Malaga (Andalusia, Spain), suggesting a founder effect in this area and describe the clinical and risk characteristics.

Lifestyle physical activity and rapid-rate non-sustained ventricular tachycardia in arrhythmogenic cardiomyopathy.

OBJECTIVE: To investigate the association of accelerometer-measured lifestyle physical activity with rapid-rate non-sustained ventricular tachycardias (RR-NSVTs) in patients with arrhythmogenic cardiomyopathy (AC). METHODS: This multicentre, observational study enrolled 72 patients with AC, including right, left and biventricular forms of the disease, with underlying desmosomal and non-desmosomal mutations. Lifestyle physical activity, objectively monitored with accelerometers (ie, movement sensors) and RR-NSVT, identified as >188 bpm and >18 beats from a textile Holter ECG for 30 days. RESULTS: Sixty-three patients with AC (38±17.6 years, 57% men) were included. A total of 17 patients experienced ≥1 RR-NSVTs, and a total of 35 events were recorded. The odds of occurrence of ≥1 RR-NSVT during the recording did not increase as a function of either total physical activity (OR 0.95, 95% CI (CI95%) 0.68 to 1.30 for 60 min increase) or moderate-to-vigorous activities (OR 0.89, CI95% 0.71 to 1.08 for 5 min increase). Participants presenting RR-NSVTs during the recording (n=17) did not present greater odds of RR-NSVT in the days with more time either in total physical activity (OR 1.05, CI95% 0.84 to 1.29 for additional 60 min) or moderate-to-vigorous activities (OR 1.05, CI95% 0.97 to 1.12 for additional 5 min). Physical activity levels were neither different between the patients with and without RR-NSVTs during the recording period nor in the days of occurrence of RR-NSVT compared with the rest of the days. Finally, 4 of the 35 RR-NSVTs recorded in the 30 days occurred during physical activity (3 during moderate-to-vigorous intensity and 1 during light-intensity activities). CONCLUSIONS: These findings suggest that lifestyle physical activity is not associated with RR-NSVTs in patients with AC.

Reablation in Atrial Fibrillation Recurrence and Pulmonary Vein Reconnection: Cryoballoon versus Radiofrequency as Index Ablation Procedures.

Pulmonary vein (PV) isolation is a well-established rhythm control therapy in atrial fibrillation (AF). Currently, there is no consensus on which ablation technique to use for the first procedure, cryoballoon (CB) or radiofrequency (RF). A retrospective cohort study was conducted on 1055 patients who underwent a first ablation, to assess both techniques based on the need for reablation. Patients with CB (n = 557) and RF (n = 498) ablations were clinically characterized and the need for reablation during a 30-month follow-up was used as the primary endpoint. Independent variables were analyzed to identify potential predictors. The need for reablation was significantly lower in the CB group than in the RF group (hazard ratio = 0.45 and 95% confident interval = 0.32−0.61; p < 0.001); in both paroxysmal and persistent AF, using a full-adjusted regression Cox model by age, sex, smoking, hypertension, diabetes mellitus, dyslipidemia, severe obstructive sleep apnea, dilated left atrium, persistent AF and early recurrence. RF ablation, dilated left atrium, persistent AF and early recurrence were identified as independent predictors of reablation. In addition, the CB-redo subgroup had a lower PV reconnection than the RF-redo subgroup. In conclusion, CB ablation suggests a reduction in the need for reablation and lower PV reconnection during the follow-up than RF ablation.

Comparison of the Use of Desflurane vs. Propofol in Aortic Valve Replacement Surgery: Differences in Nephroprotection: An Explorative and Hypothesis-Generating Study.

Introduction: The cardioprotective effect of halogenated drugs in cardiac surgery has been the subject of several studies. However, there is scarcity of data on their potential nephroprotective effects. Aortic valve replacement and coronary revascularization are the most frequent cardiac surgery procedures. The objective of this explorative study was to examine the effect of desflurane vs. propofol on renal function, when administered in aortic valve replacement surgery, including the extracorporeal circulation period. Method: A quasi-experimental prospective study was performed in 60 patients, who were allocated to receive either desflurane or propofol intraoperatively during aortic valve replacement surgery. As a hypnotic, group 1 received propofol, whereas group 2 received desflurane. Markers of renal function and level of cardiac preservation were determined based on biochemical parameters (troponin I, NTProBNP). Results: In the propofol group, there were significant variations between postoperative values of urinary NGAL and creatinine and baseline values. In contrast, no variations were found in the desflurane group in terms of hemodynamic parameters and myocardial damage. Conclusions: The use of propofol vs. desflurane during aortic valve replacement surgery is associated with a decrease in renal function.

Overexpression of scavenger receptor and infiltration of macrophage in epicardial adipose tissue of patients with ischemic heart disease and diabetes.

BACKGROUND: Oxidized low-density lipoproteins and scavenger receptors (SRs) play an important role in the formation and development of atherosclerotic plaques. However, little is known about their presence in epicardial adipose tissue (EAT). The objective of the study was to evaluate the mRNA expression of different SRs in EAT of patients with ischemic heart disease (IHD), stratifying by diabetes status and its association with clinical and biochemical variables. METHODS: We analyzed the mRNA expression of SRs (LOX-1, MSR1, CXCL16, CD36 and CL-P1) and macrophage markers (CD68, CD11c and CD206) in EAT from 45 patients with IHD (23 with type 2 diabetes mellitus (T2DM) and 22 without T2DM) and 23 controls without IHD or T2DM. RESULTS: LOX-1, CL-P1, CD68 and CD11c mRNA expression were significantly higher in diabetic patients with IHD when compared with those without T2DM and control patients. MSR1, CXCL16, CD36 and CD206 showed no significant differences. In IHD patients, LOX-1 (OR 2.9; 95% CI 1.6-6.7; P = 0.019) and CD68 mRNA expression (OR 1.7; 95% CI 0.98-4.5; P = 0.049) were identified as independent risk factors associated with T2DM. Glucose and glycated hemoglobin were also shown to be risk factors. CONCLUSIONS: SRs mRNA expression is found in EAT. LOX-1 and CD68 and were higher in IHD patients with T2DM and were identified as a cardiovascular risk factor of T2DM. This study suggests the importance of EAT in coronary atherosclerosis among patients with T2DM.

Rentabilidad del estudio genético mediante técnicas de next-generation sequencing masiva de pacientes con miocardiopatía arritmogénica de alto riesgo / Usefulness of genetic study by next-generation sequencing in high-risk arrhythmogenic cardiomyopathy

Introducción y objetivos: La miocardiopatía arritmogénica del ventrículo derecho (MCAVD) es una cardiopatía hereditaria definida por la sustitución progresiva de miocardio ventricular derecho por tejido fibroadiposo. Es causa frecuente de la muerte súbita de jóvenes atletas. El objetivo del presente estudio es conocer la incidencia de variantes desmosómicas patogénicas o probablemente patogénicas en pacientes con MCAVD definitiva de alto riesgo. Métodos: El estudio de cohortes retrospectivo observacional incluyó a 36 pacientes diagnosticados de MCAVD definitiva de alto riesgo en nuestro hospital entre enero de 1998 y enero de 2015. El análisis genético se realizó con next-generation sequencing. Resultados: La mayoría eran varones (28 pacientes, 78%) con una media de edad al diagnóstico de 45 ± 18 años. Se detectó al menos 1 variante desmosómica patogénica o probablemente patogénica en 26 de los 35 casos índice (74%): 5 nonsense, 14 frameshift, 1 splice y 6 missense. En 15 pacientes (71%) se encontraron mutaciones nuevas. La presencia o la ausencia de mutaciones desmosómicas o la naturaleza de estas no se asociaron con características electrocardiográficas, clínicas, arrítmicas, anatómicas o pronósticas específicas. Conclusiones: La incidencia de variantes desmosómicas patogénicas o probablemente patogénicas en MCAVD definitiva de alto riesgo fue muy alta, con mayoría de mutaciones que causan truncamiento. La presencia de mutaciones desmosómicas no se asoció con el pronóstico

Introduction and objectives: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium. This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC. Methods: This was an observational, retrospective cohort study, which included 36 patients diagnosed with high-risk ARVC in our hospital between January 1998 and January 2015. Genetic analysis was performed using next-generation sequencing. Results: Most patients were male (28 patients, 78%) with a mean age at diagnosis of 45 ± 18 years. A pathogenic or probably pathogenic desmosomal mutation was detected in 26 of the 35 index cases (74%): 5 nonsense, 14 frameshift, 1 splice, and 6 missense. Novel mutations were found in 15 patients (71%). The presence or absence of desmosomal mutations causing the disease and the type of mutation were not associated with specific electrocardiographic, clinical, arrhythmic, anatomic, or prognostic characteristics. Conclusions: The incidence of pathological or likely pathological desmosomal mutations in ARVC is very high, with most mutations causing truncation. The presence of desmosomal mutations was not associated with prognosis

Impact of dynamic physical exercise on high-risk definite arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiomyopathy characterized by ventricular arrhythmias and heart failure. The variable phenotype suggesting that determined environmental factors may have an influence. The aim of our study was to discover the impact of the dynamic physical activity on patients with high-risk definite ARVC/D. METHODS AND RESULTS: Collection of data on physical activity at the time of diagnosis was conducted at an in-person clinical interview. The intensity of the activity was classified in accordance with the mean frequency of weekly physical exercise sessions in the 10 years before diagnosis and into the following three groups of dynamic activity: high/competitive (>3 h/wk), moderate (1 to 3 h) and minimal/inactive (<1 h). Seventeen patients practiced high dynamic physical activities. The intensity of dynamic activity was classified into three groups: 8 of high intensity, 9 moderate, and 19 inactive. The first major arrhythmic event and occurrence of severe right ventricular dysfunction were earlier in the high-intensity exercise group, followed by the moderate intensity group and at a later age in the low-intensity/inactive group. CONCLUSIONS: Dynamic exercise could be directly associated with the severity of the phenotype in relation to the precocity of major ventricular arrhythmic events and right ventricular systolic dysfunction in patients with high-risk definite ARVC/D.

Usefulness of Genetic Study by Next-generation Sequencing in High-risk Arrhythmogenic Cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium. This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC. METHODS: This was an observational, retrospective cohort study, which included 36 patients diagnosed with high-risk ARVC in our hospital between January 1998 and January 2015. Genetic analysis was performed using next-generation sequencing. RESULTS: Most patients were male (28 patients, 78%) with a mean age at diagnosis of 45 ± 18 years. A pathogenic or probably pathogenic desmosomal mutation was detected in 26 of the 35 index cases (74%): 5 nonsense, 14 frameshift, 1 splice, and 6 missense. Novel mutations were found in 15 patients (71%). The presence or absence of desmosomal mutations causing the disease and the type of mutation were not associated with specific electrocardiographic, clinical, arrhythmic, anatomic, or prognostic characteristics. CONCLUSIONS: The incidence of pathological or likely pathological desmosomal mutations in ARVC is very high, with most mutations causing truncation. The presence of desmosomal mutations was not associated with prognosis.

Expression of Sterol Regulatory Element-Binding Proteins in epicardial adipose tissue in patients with coronary artery disease and diabetes mellitus: preliminary study.

Objectives: Sterol regulatory element-binding proteins (SREBP) genes are crucial in lipid biosynthesis and cardiovascular homeostasis. Their expression in epicardial adipose tissue (EAT) and their influence in the development of coronary artery disease (CAD) and type-2 diabetes mellitus remain to be determined. The aim of our study was to evaluate the expression of SREBP genes in EAT in patients with CAD according to diabetes status and its association with clinical and biochemical data. Methods: SREBP-1 and SREBP-2 mRNA expression levels were measured in EAT from 49 patients with CAD (26 with diabetes) and 23 controls without CAD or diabetes. Results: Both SREBPs mRNA expression were significantly higher in patients with CAD and diabetes (p<0.001) and were identified as independent cardiovascular risk factor for coronary artery disease in patients with type-2 diabetes (SREBP-1: OR 1.7, 95%CI 1.1-2.5, p=0.02; SREBP-2: OR 1.6, 95%CI 1.2-3, p=0.02) and were independently associated with the presence of multivessel CAD, left main and anterior descending artery stenosis, and higher total and LDL cholesterol levels, and lower HDL cholesterol levels, in patients with CAD and diabetes. Conclusions: SREBP genes are expressed in EAT and were higher in CAD patients with diabetes than those patients without CAD or diabetes. SREBP expression was associated as cardiovascular risk factor for the severity of CAD and the poor lipid control. In this preliminary study we suggest the importance of EAT in the lipid metabolism and cardiovascular homeostasis for coronary atherosclerosis of patients with diabetes and highlight a future novel therapeutic target.

Comparison of the new risk prediction model (HCM Risk-SCD) and classic risk factors for sudden death in patients with hypertrophic cardiomyopathy and defibrillator.

AIMS: Hypertrophic cardiomyopathy is one of the main causes of sudden death in young people. Recent clinical practice guidelines include a risk prediction model for sudden death (HCM Risk-SCD), which facilitates the decision of whether to implant a defibrillator. The aim of our study was to ascertain the percentage of events in our series of primary prevention implantable cardioverter-defibrillator recipients with hypertrophic cardiomyopathy and whether HCM Risk-SCD predicts the onset of arrhythmic events. METHODS AND RESULTS: This was an observational, retrospective cohort study, which included 48 primary prevention defibrillator recipient patients with HCM. We compiled their demographic and clinical characteristics, estimated 5-year risk using HCM Risk-SCD, and collected the documentation on arrhythmias during follow-up. The majority was male (66.7%) and mean age at implantation was 44.44 ± 14.46 years. Non-sustained ventricular tachycardia was the most prevalent risk factor (66.67%), followed by a family history of sudden death (47.92%). Mean HCM Risk-SCD was 6.15 ± 5.01%. HCM Risk-SCD was the only factor independently associated with the onset of ventricular tachyarrhythmia, above any other classic risk factor or association [odds ratio = 1.46 (95% confidence interval 1.051-2.013); P = 0.02]. None of the 11 patients estimated as low risk using HCM Risk-SCD suffered any appropriate events (P < 0.05). CONCLUSIONS: During an average follow-up of 4 years, 16.67% presented appropriate events (4.16%/year). HCM Risk-SCD predicted the onset of events more suitably than classic risk factors.

Serum levels of interleukin-2 predict the recurrence of atrial fibrillation after pulmonary vein ablation.

AIMS: Interleukin-2 has a significant antitumor activity in some types of cancer, and has been associated with the development of atrial fibrillation (AF). In addition, IL-2 serum levels in recent onset AF have been related with pharmaceutical cardioversion outcomes. We evaluated the hypothesis that a relationship exists between inflammation and the outcome of catheter ablation of AF. METHODS: We studied 44 patients with paroxysmal AF who underwent catheter ablation. Patients with structural heart disease, coronary artery or valve disease, active inflammatory disease, known or suspected neoplasm, endocrinopathies, or exposure to anti-inflammatory drugs were excluded. All study participants underwent evaluation with a standardized protocol, including echocardiography, and cytokine levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumour necrosis factor-alpha, and gamma-interferon determination before procedure. Clinical and electrocardiographic follow-up were performed with Holter-ECG at 3, 6 and 12months in order to know if sinus rhythm was maintained. RESULTS: After catheter ablation of the 44 patients included (53±10years, 27.3% female), all patients returned to sinus rhythm. During the first year of follow-up seven patients (15.9%) experienced recurrence of AF. The demographics, clinical and echocardiographic features, and pharmacological treatments of these patients were similar to those who maintained sinus rhythm. The only independent factor predictive of recurrence of AF was an elevated level of IL-2 (OR 1.18, 95% CI 1.12-1.38). CONCLUSIONS: High serum levels of interleukin-2, a pro-inflammatory non-vascular cytokine, are associated with the recurrence of AF in patients undergoing catheter ablation.

Relación entre cistatina C y calcificación coronaria en pacientes con riesgo cardiovascular intermedio / Relationship between cystatin C and coronary artery calcification in patients with intermediate cardiovascular risk

Fundamento y objetivo: La enfermedad cardiovascular es la principal causa de morbimortalidad en los países industrializados. La cuantificación del calcio arterial coronario (CAC) ha demostrado tener un valor pronóstico independiente e incremental con respecto a los factores de riesgo tradicionales para la predicción de mortalidad y episodios cardiovasculares. El objetivo de nuestro estudio fue determinar la posible relación entre el CAC y la cistatina C (CTC). Pacientes y método: Se incluyeron 104 pacientes con dolor torácico estable, libres de enfermedad cardiovascular y nefropatía, con riesgo cardiovascular intermedio, en los que se determinaron el CAC (Agatston) y CTC. Resultados: La CTC se asoció de forma independiente respecto a los factores de riesgo clásicos con el nivel de CAC y con la presencia de enfermedad coronaria. Conclusiones: Los valores de CTC podrían asociarse con el CAC y con el riesgo de enfermedad coronaria. Es necesaria la aparición de nuevos estudios para conocer la importancia de estos marcadores en la práctica clínica habitual (AU)

Background and objective: Cardiovascular disease is the leading cause of morbimortality in industrialized countries. Quantification of coronary artery calcium (CAC) has been shown to have an independent and incremental prognostic value over traditional risk factors for the prediction of mortality and cardiovascular events. The aim of our study was to determine the possible relationship between CAC and cystatin C (CTC). Patients and method: We included 104 patients with stable chest pain, free of cardiovascular disease and nephropathy, with intermediate cardiovascular risk. Both CAC (Agatston) and CTC were determined. Results: CTC was independently associated with the CAC level and the presence of coronary disease. Conclusions: CTC values may be associated with CAC and coronary disease. Further studies are needed to know the importance of these markers in clinical practice (AU)

[Relationship between cystatin C and coronary artery calcification in patients with intermediate cardiovascular risk]. / Relación entre cistatina C y calcificación coronaria en pacientes con riesgo cardiovascular intermedio.

BACKGROUND AND OBJECTIVE: Cardiovascular disease is the leading cause of morbimortality in industrialized countries. Quantification of coronary artery calcium (CAC) has been shown to have an independent and incremental prognostic value over traditional risk factors for the prediction of mortality and cardiovascular events. The aim of our study was to determine the possible relationship between CAC and cystatin C (CTC). PATIENTS AND METHOD: We included 104 patients with stable chest pain, free of cardiovascular disease and nephropathy, with intermediate cardiovascular risk. Both CAC (Agatston) and CTC were determined. RESULTS: CTC was independently associated with the CAC level and the presence of coronary disease. CONCLUSIONS: CTC values may be associated with CAC and coronary disease. Further studies are needed to know the importance of these markers in clinical practice.