Role of Soluble ST2 Biomarker in Predicting Recurrence of Atrial Fibrillation after Electrical Cardioversion or Pulmonary Vein Isolation.

This study aims to determine the predictive value of the soluble suppression of tumorigenicity 2 (sST2) biomarker in atrial fibrillation (AF) recurrence. This prospective, observational study included patients with AF referred for electrical cardioversion (ECV) or pulmonary vein isolation (PVI) procedures. Baseline characteristics were collected, and sST2 was determined at baseline and at 3 and 6 months of follow-up. sST2 was determined at baseline in a matched control group. Left atrial voltage mapping was performed in patients undergoing PVI. The sST2 maximal predictive capacity of AF recurrence was at the 3-month FU in the cohort of patients undergoing ECV with respect to 6-month AF recurrence with an AUC of 0.669, a cut-off point of 15,511 pg/mL, a sensitivity of 60.97%, and a specificity of 69.81%. The ROC curve of the sST2 biomarker at baseline and 3 months in the cohort of patients undergoing PVI showed AUCs of 0.539 and 0.490, respectively. The logistic regression model identified the rhythm (AF) and the sST2 biomarker at 3 months as independent factors for recurrence at 6 months in the ECV cohort. In the logistic regression model, sST2 was not an independent factor for recurrence at 6 months of follow-up in the PVI cohort. In patients who underwent ECV, sST2 values at 3 months may provide utility to predict AF recurrence at 6 months of follow-up. In patients who underwent PVI, sST2 had no value in predicting AF recurrence at 6 months of follow-up.

Circulating miR-451a Expression May Predict Recurrence in Atrial Fibrillation Patients after Catheter Pulmonary Vein Ablation.

Atrial fibrillation is the most prevalent tachyarrhythmia in clinical practice, with very high cardiovascular morbidity and mortality with a high-cost impact in health systems. Currently, it is one of the main causes of stroke and subsequent heart failure and sudden death. miRNAs mediate in several processes involved in cardiovascular disease, including fibrosis and electrical and structural remodeling. Several studies suggest a key role of miRNAs in the course and maintenance of atrial fibrillation. In our study, we aimed to identify the differential expression of circulating miRNAs and their predictive value as biomarkers of recurrence in atrial fibrillation patients undergoing catheter pulmonary vein ablation. To this effect, 42 atrial fibrillation patients were recruited for catheter ablation. We measured the expression of 84 miRNAs in non-recurrent and recurrent groups (45.2%), both in plasma from peripheral and left atrium blood. Expression analysis showed that miRNA-451a is downregulated in recurrent patients. Receiver operating characteristic curve analysis showed that miR-451a in left atrium plasma could predict atrial fibrillation recurrence after pulmonary vein isolation. In addition, atrial fibrillation recurrence is positively associated with the increment of scar percentage. Our data suggest that miRNA-451a expression plays an important role in AF recurrence by controlling fibrosis and progression.

Circulating miR-499a and miR-125b as Potential Predictors of Left Ventricular Ejection Fraction Improvement after Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy represents a therapeutic option for heart failure drug-refractory patients. However, due to the lack of success in 30% of the cases, there is a demand for an in-depth analysis of individual heterogeneity. In this study, we aimed to evaluate the prognostic value of circulating miRNA differences. Responder patients were defined by a composite endpoint of the presence of left ventricular reverse remodelling (a reduction ≥15% in telesystolic volume and an increment ≥10% in left ventricular ejection fraction). Circulating miRNAs signature was analysed at the time of the procedure and at a 6-month follow-up. An expression analysis showed, both at baseline and at follow-up, differences between responders and non-responders. Responders presented lower baseline expressions of miR-499, and at follow-up, downregulation of miR-125b-5p, both associated with a significant improvement in left ventricular ejection fraction. The miRNA profile differences showed a marked sensitivity to distinguish between responders and non-responders. Our data suggest that miRNA differences might contribute to prognostic stratification of patients undergoing cardiac resynchronization therapy and suggest that preimplant cardiac context as well as remodelling response are key to therapeutic success.

Long-term cardiac reverse remodeling after cardiac resynchronization therapy.

INTRODUCTION: The benefit of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF) have been observed in the first year. However, there are few data on long-term follow-up and the effect of changes of LVEF on mortality. This study aimed to assess the LV remodeling after CRT implantation and the probable effect of changes in LVEF with repeated measures on mortality over time in a real-world registry. METHODS: Among our cohort of 328 consecutive CRT patients, mixed model effect analysis have been made to describe the temporal evolution of LVEF and LVESV changes over time up with several explanatory variables. Besides, the effect of LVEF along time on the probability of mortality was evaluated using joint modeling for longitudinal and survival data. RESULTS: The study population included 328 patients (253 men; 70.2 ± 9.5 years) in 4.2 (2.9) years follow-up. There was an increase in LVEF of 11% and a reduction in LVESV of 42 mL during the first year. These changes are more important during the first year, but slight changes remain during the follow-up. The largest reduction in LVESV occurred in patients with left bundle branch block (LBBB) and the smallest reduction in patients with NYHA IV. The smallest increase in LVEF was an ischemic etiology, longer QRS, and LV electrode in a nonlateral vein. Besides, the results showed that the LVEF profiles taken during follow-up after CRT were associated with changes in the risk of death. CONCLUSION: Reverse remodeling of the left ventricle is observed especially during the first year, but it seems to be maintained later after CRT implantation in a contemporary cohort of patients. Longitudinal measurements could give us additional information at predicting the individual mortality risk after adjusting by age and sex compared to a single LVEF measurement after CRT.

Conventional single-chamber pacemakers versus transcatheter pacing systems in a "real world" cohort of patients: A comparative prospective single-center study.

PURPOSE: Despite the developments in conventional transvenous pacemakers (VVI-PM), the procedure is still associated with significant complications. Although there are no prospective clinical trials that compared VVI-PM with transcatheter pacemaker systems (TPS). METHODS: This is a prospective, observational, single-center study that included all patients with an indication for a single-chamber pacemaker implant within a 4-year period. All clinical, ECG and echocardiographic characteristics at implant, electrical parameters, associated complications and mortality were analyzed. A Cox survival model and a Bayesian cohort analysis were performed for differences in complication rates between groups. RESULTS: There were 443 patients included (198 TPS and 245 VVI-PM). The mean age was 81.5 years (TPS group, 79.2 ± 6.6 years; VVI-PM group, 83.5 ± 8.9 years). There was a male predominance in TPS group (123, 62.1% vs. 67, 27.3%; p < 0.001). The presence of systolic dysfunction and renal insufficiency were more frequent in VVI-PM group than in TPS patients. Mean follow-up was 22.3 ± 15.9 months. In a multivariable paired data the TPS group presented fewer complications than VVI-PM group (HR = 0.39 [0.15-0.98], p-value 0.013), but major complications were not different (6, 3% vs 14, 5.6% respectively, p = 0.1761). There was no difference in the mortality rate between the groups. The TPS group had less risk than VVI-PM group to have a complication, with a 96% of probability. CONCLUSIONS: TPS patients had a lower overall complication rate than VVI-PM patients including matched-pair samples using a Bayesian analysis. These results confirm the safety profile of TPS in clinical practice.

Use of an angioplasty wire in transseptal puncture: A new application of an old technique.

OBJECTIVE: We wondered if a modification of the conventional transseptal puncture technique performed with an angioplasty wire could be useful in patients with contrast hypersensitivity or allergy-like reactions. METHODS: This study comprised our initial experience in 22 patients with atrial fibrillation who were scheduled for an electrophysiology study (EPS) and pulmonary vein ablation and who had a contraindication for iodinated contrast administration. RESULTS: Of the 22 patients, 16 were men and ages ranged from 27 to 74 years (mean 56 years). Overall successful transseptal access was achieved in all 22. A control echocardiogram was performed in all patients. There were no complications in any case and no significant differences were found from the conventional transseptal puncture technique regarding procedure or fluoroscopy time. CONCLUSIONS: A modification of the conventional transseptal puncture technique performed with fluoroscopy and EPS catheters for anatomical reference and an angioplasty wire is an option in cases with severe contrast hypersensitivity.

Ablation of atrial fibrillation in patients with Brugada syndrome: A systematic review of the literature.

Supraventricular arrhythmias are common in Brugada syndrome (BS), and notoriously difficult to manage with medical therapy secondary to associated risks. Pulmonary vein isolation (PVI) is often utilized instead, but its outcomes in this population are not well-known. We aim to provide a holistic evaluation of interventional treatment for Atrial fibrillation (AF) in the BS population. Electronic databases Medline, Embase, Cinahl, Cochrane, and Scopus were systematically searched for publications between 01/01/1995 and 12/31/2017. Studies were screened based on predefined inclusion and exclusion criteria. A total of 49 patients with BS and AF were included. Age range from 28.8 to 64 years, and 77.5% were male. 38 patients were implanted with implantable cardioverter-defibrillators (ICD) at baseline, and of them, 39% suffered inappropriate shocks for rapid AF. 34/49 (69%) of patients achieved remission following a single PVI procedure. Of the remaining, 13 patients underwent one or more repeat ablation procedures. Overall, 45/49 (91.8%) of patients remained in remission during long-term follow-up after one or more PVI procedures in the absence of antiarrhythmic drug (AAD) therapy. Postablation, no patients suffered inappropriate ICD shock. Furthermore, no major complications secondary to PVI occurred in any patient. AF ablation achieves acute and long-term success in the vast majority of patients. It is effective in preventing inappropriate ICD therapy secondary to rapid AF. Complication rates of PVI in BS are low. Thus, in light of the risks of AADs and risk of inappropriate ICD shocks in the BS population, catheter ablation could represent an appropriate first-line therapy for paroxysmal atrial fibrillation in BS patients.

Cholinergic activity regulates the secretome of epicardial adipose tissue: Association with atrial fibrillation.

Botulinum toxin injection on epicardial fat, which inhibits acetylcholine (ACh) release, reduced the presence of atrial fibrillation (AF) in patients after heart surgery. Thus, we wanted to study the profile of the released proteins of epicardial adipose tissue (EAT) under cholinergic activity (ACh treatment) and their value as AF predictors. Biopsies, explants, or primary cultures were obtained from the EAT of 85 patients that underwent open heart surgery. The quantification of muscarinic receptors (mAChR) by real-time polymerase chain reaction or western blot showed their expression in EAT. Moreover, mAChR Type 3 was upregulated after adipogenesis induction (p < 0.05). Cholinergic fibers in EAT were detected by vesicular ACh transporter levels and/or acetylcholinesterase activity. ACh treatment modified the released proteins by EAT, which were identified by nano-high-performance liquid chromatography and TripleTOF analysis. These differentially released proteins were involved in cell structure, inflammation, or detoxification. After testing the plasma levels of alpha-defensin 3 (inflammation-involved protein) of patients who underwent open heart surgery ( n = 24), we observed differential levels between the patients who developed or did not develop postsurgery AF (1.58 ± 1.61 ng/ml vs. 6.2 ± 5.6 ng/ml; p < 0.005). The cholinergic activity on EAT might suggest a new mechanism for studying the interplay among EAT, autonomic nervous system dysfunction, and AF.

Respuesta al ECG de octubre de 2018 / Response to ECG, October 2018

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Cardiac resynchronization therapy outcomes in patients under nonoptimal medical therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is indicated in symptomatic heart failure (HF) patients after achieving optimal medical therapy (OMT). However, many patients may not be under OMT when the CRT device is implanted. Here, we evaluate the long-term benefits of CRT in symptomatic HF patients receiving or not OMT. METHODS: We investigated the effect of OMT on HF developing or death in 328 consecutive patients with a CRT device implanted between 2005 and 2015 in a single tertiary center. After the CRT implant, we categorized the patients into three groups: no OMT, OMT at baseline and after 1 year of follow-up, and OMT only at the 1-year follow-up but not at baseline. We used multivariate Cox proportional hazards model to determine the effect of OMT on clinical outcomes. RESULTS: One hundred and twenty-two patients (37.2%) received OMT prior to CRT. OMT at baseline was not associated with a reduced risk of death or HF (HR 0.72; 95% CI 0.50-1.02; P = 0.067) compared with no-basal-OMT patients. After CRT, patients without OMT had a higher risk of death or HF than patients who received OMT in follow-up (HR 1.72, 95% CI 1.07-2.78, P = 0.025), and the risk of the patients who received OMT at baseline and at the 1-year follow-up was similar to that of the patients who achieved OMT at the 1-year follow-up (HR 0.90, 95% CI 0.54-1.50, P = 0.682). CONCLUSION: Basal OMT prior to CRT is not associated with better outcomes in terms of HF/death compared with no basal OMT. The subgroup of patients who achieved OMT at the 1-year follow-up exhibited a reduced risk of HF and death compared with patients who did not.

ECG de octubre de 2018 / ECG, October 2018

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Cardiac resynchronization therapy response in heart failure patients with different subtypes of true left bundle branch block.

PURPOSE: Left bundle branch block (LBBB) configuration has been described as a predictor of response to cardiac resynchronization therapy (CRT). We investigated whether different subtypes of true LBBB configuration could help select patients with better response and clinical outcome. METHODS: This retrospective study included 198 consecutive LBBB patients implanted with a CRT. True LBBB was defined using the Strauss and the Predict study criteria. Echocardiographic response was evaluated by the reduction in left ventricular end-systolic volume (LVESV) and the increase in left ventricular ejection fraction (LVEF). Clinical response was defined as an improvement in one category of the NYHA functional class. RESULTS: Patients with true LBBB had a greater improvement in both LVESV reduction (median = - 27.6%, interquartile range = [- 4.9, - 50.1]) and LVEF increase (median 10.8 ± 10) than those with non-true LBBB (- 19.7%, [16.7, - 48.0]) p = 0.04 and 5.1 ± 10, p = 0.03, respectively. No differences were exhibited between true LBBB Strauss group (- 26.7%, [- 11.0, - 46.9]) and true LBBB Predict group (- 26.6%, [- 15.9, - 39.4]). There were no statistically significant differences in the percentage of patients with clinical response, assessed by NYHA improvement, among all groups. In the Cox model for death, age, ischemic etiology, and ΔLVESV were independent predictors of mortality. True LBBB (Strauss + Predict) patients had a trend towards lower mortality than non-true LBBB [HR = 0.55, 95% CI = (0.22-1.15)], p = 0.08. In the Cox model for HF hospitalization, age, sex male, prior LVEF, and ΔLVESV were independent predictors. True LBBB (Strauss + Predict) patients had a significantly lower risk of developing HF hospitalization than those with non-true LBBB [0.45 (0.21-0.90)], p = 0.029. CONCLUSIONS: Patients with true LBBB, either Strauss or Predict criteria, had greater echocardiographic response and lower incidence of HF hospitalization than non-true LBBB when implanted with CRT.

Prognostic value of nutrition status in the response of cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is indicated in symptomatic heart failure (HF) patients after achieving optimal medical therapy. However, there are still a large percentage of patients who do not respond to CRT. Malnutrition is a frequent comorbidity in patients with HF, and it is associated with a poorer prognosis. Here, we evaluate the nutritional status of patients assessed by Controlling Nutritional Status (CONUT) score and its association with structural remodeling and cardiovascular events. METHODS: We investigated the effect of CONUT on HF/death in 302 consecutive patients with a CRT device implanted between 2005 and 2015 in a single tertiary center. We categorized the patients into three groups: normal nutritional status (CONUT 0-1), mild malnutrition (CONUT 2-4) and moderate-severe malnutrition (CONUT ≥ 5). Changes in nutritional status were assessed in patients with mild-to-severe malnutrition prior to CRT. RESULTS: One hundred and forty-eight patients exhibited normal nutritional status (49.0%), 99 patients exhibited mild malnutrition (32.8%) and 55 patients exhibited moderate-severe malnutrition (18.2%). CONUT scores of at least 2 were associated with higher risk of HF/death compared with CONUT 0-1. Significant left ventricular (LV) reverse remodeling was noted in patients with better nutritional status. In addition, those malnutrition patients at baseline that improved nutritional state exhibited fewer HF/death events at follow-up. CONCLUSION: CONUT score prior to CRT was an independent risk factor of death/HF and was correlated with LV reverse remodeling. Improvements in CONUT score during long-term follow-up were associated with a reduction in the rate of HF/death.

Comparison and Validation of Recommended QT Interval Correction Formulas for Predicting Cardiac Arrhythmias in Patients With Advanced Heart Failure and Cardiac Resynchronization Devices.

QT interval prolongation is an important marker for the development of cardiac arrhythmias (CAs). Optimal methods to estimate QT/QTc intervals in patients with ventricular pacing (VP) and its correlation with CA have not been widely investigated. We aimed to validate the currently available formulas for QT determination during VP and to compare their abilities in predicting the occurrence of CA (atrial fibrillation [AF] and malignant ventricular arrhythmias [VAs] in patients with advanced heart failure and cardiac resynchronization therapy). Consecutive patients with advanced heart failure who underwent cardiac resynchronization therapy implantation between August 2001 and April 2015 were included in a retrospective study. Four proposed formulas for QT correction in VP rhythms were evaluated. One hundred eighty patients were enrolled. During 44 months of follow-up, 43 patients (37.7%) developed AF and 16 patients (8.9%) developed VA. There was no correlation between corrected QT increments and AF risk with any of the formulas for paced rhythms. Regarding VA, higher corrected QT values measured with Massachusetts' formula (QTcM) were found to have a higher risk of event (p = 0.036) (Beta = 1.012 [1.001 to 1.023]). Each 1 ms increase in QTc increased the probability of experiencing VA by 12‰. QTcM >444 was found to be a strong predictor of VA. In conclusion, there are significant differences in mean QTc interval measured by the currently advised formulas. QTc interval was not associated with AF in any of the formulas. Only the QTcM formula showed a significant stepwise increase in the risk of experiencing malignant VA.

Marcapasos transcatéter sin cables Micra. Resultados del implante y seguimiento a medio plazo en un centro / The micra leadless transcatheter pacemaker. implantation and mid-term follow-up results in a single center

Introducción y objetivos: Actualmente hay pocos estudios sobre el marcapasos sin cable (Micra) en la práctica clínica, especialmente con seguimientos > 6 meses. El objetivo es evaluar los parámetros eléctricos al implante y en el seguimiento, así como la seguridad de esta nueva técnica. Métodos: Estudio prospectivo y observacional en el que se incluyó a 30 pacientes consecutivos de edad ≥ 65 años con indicación de implante de marcapasos unicameral. Resultados: Se implantó exitosamente el Micra en los 30 pacientes incluidos. La media de edad era 79,4 ± 6,4 (66-89) años; 20 (66,6%) eran varones; 28 (93,3%) presentaban fibrilación auricular permanente; 1, taquicardia auricular y 1, ritmo sinusal. En 5 pacientes (16,6%) se realizó ablación del nódulo auriculoventricular en el mismo procedimiento (4 pacientes en fibrilación auricular rápida y 1 con taquicardia auricular); en 2 pacientes la indicación fue tras el implante percutáneo de válvula aórtica. En 23 (76,6%) el implante se realizó estando en tratamiento anticoagulante oral (INR máximo, 2,4). No hubo complicaciones mayores, salvo un derrame pericárdico moderado sin repercusión hemodinámica. El seguimiento medio fue de 5,3 ± 3,3 meses y 4 pacientes superaron el año de seguimiento. Los parámetros de estimulación fueron excelentes tanto en el implante como en el seguimiento a corto-medio plazo. Conclusiones: El implante de marcapasos sin cables es factible y seguro y presenta potenciales ventajas sobre los sistemas convencionales. Serán necesarios estudios con mayor seguimiento antes de generalizar su uso en la práctica clínica diaria (AU)

Introduction and objectives: Currently, studies on the leadless pacemaker (Micra) have mostly been limited to clinical trials with less than 6 months’ follow-up and they often fail to reflect real population outcomes. We sought to evaluate electrical parameters at implantation and chronologically during follow-up, as well as the safety of this new technique. Methods: This prospective, observational study included 30 consecutive patients, all ≥ 65 years, with an indication for single-chamber pacemaker implantation. Results: Successful implantation was accomplished in all patients referred for leadless implantation. The mean age was 79.4 ± 6.4 years (range, 66-89 years); 20 (66.6%) were men and 28 had permanent atrial fibrillation (93.3%); 1 had atrial tachycardia and 1 had sinus rhythm. Concomitant atrioventricular node ablation was performed immediately after implantation in 5 patients (16.6%), and implantation was performed after transcatheter aortic valve implantation in 2. The procedure was performed under an uninterrupted anticoagulation regimen (maximum INR 2.4) in 23 patients (76.6%). With the exception of 1 moderate pericardial effusion without tamponade, there were no severe complications. The mean follow-up was 5.3 ± 3.3 months and 4 patients had more than 1 year of follow-up. Sensing and pacing parameters were stable both at implantation and during the short- to mid-term follow-up. Conclusions Implantation of leadless pacemakers is feasible, safe and provides advantages over the conventional system. Further studies with longer follow-up periods will be needed before these devices become widely used in routine clinical practice (AU)