The Effects of Different Hormones on Supraventricular and Ventricular Premature Contractions in Healthy Premenopausal Women.

Background and Objectives: The effects of gender differences on cardiac parameters have been well-established. In this study, we aimed to evaluate the possible associations of plasma levels of different sex hormones with premature atrial or ventricular contractions in premenopausal women. Materials and Methods: We conducted a prospective study which included women in late reproductive age who presented with palpitations during an eight-month period. A 12-lead electrocardiography, a transthoracic echocardiogram, blood samples, and 24-hour rhythm Holter were conducted on the third day of the menstrual cycle. Results Overall, 93 healthy premenopausal women with a median age of 42 years were enrolled. QTc interval was within normal limits in all patients. The 24 h range of premature atrial contractions (PACs) and premature ventricular contractions (PVCs) was 0-6450 and was 0-21,230, respectively. The median number of PVCs was 540 and the median number of PACs was 212, respectively. In total, 51 patients (54.8%) had a frequency of PVCs > 500/24 h and 37 patients (39.8%) had a frequency of PACs > 500/24 h, respectively. No statistically significant association was shown between any hormone and the frequency of PACs. Regarding PVCs, patients with a PVCs frequency > 500/24 h had higher estradiol levels compared to patients with PVCs less than 500/24 h (median 60 pg/mL versus 42 pg/mL, p = 0.02, OR: 1.01). No association was found between PVCs and other hormones. Conclusions: In premenopausal healthy women, higher estradiol levels are independently associated with increased PVCs. This suggests that estradiol in late reproductive stages may exert proarrhythmic effects.

Targeted ablation of specific electrogram patterns in low-voltage areas after pulmonary vein antral isolation in persistent atrial fibrillation: Termination to an organized rhythm reduces atrial fibrillation recurrence.

BACKGROUND: Ablation strategies have been developed to improve outcomes in patients with persistent atrial fibrillation (PsAF). However, the impact of atrial fibrillation (AF) termination on late AF recurrence is not well known. The aim of our study was to evaluate the impact of AF termination to atrial tachycardia (AT) or sinus rhythm (SR) during catheter ablation on late AF recurrence after the 3-month blanking period. METHODS AND RESULTS: We prospectively recruited 140 patients (mean age: 58.5 ± 12.3 years old, 74.3% males) with uninterrupted PsAF of a mean duration of 3.7 months. Pulmonary vein antral isolation (PVAI) was the first ablation step, and if AF did not terminate (to SR or AT), we ablated low-voltage areas less than 0.4 mV with specific electrogram characteristics. We successfully converted AF to AT or SR in 56 patients (40%) during PVAI (n = 24) or low-voltage ablation ( n = 32). The remaining 84 patients (60%) were electrically cardioverted to SR at the end of the procedure. One hundred patients (71.4%) maintained SR after a single procedure during a mean follow-up of 21.1 ± 0.8 months. Of the 56 patients with AF termination, 46 (82.1%) had no recurrence, while in the group of 84 patients without AF termination, 54 patients (64.3%) remained in SR ( P < 0.02). CONCLUSION: Ablation of PVAI and specific electrograms in low-voltage areas less than 0.4 mV can lead to encouraging outcomes with a low recurrence rate as well as a lower need for redo procedures.

Implantable devices to monitor patients with heart failure.

Reducing heart failure hospitalizations represents a major challenge for modern clinicians. Early detection of congestion plays a key role in disease management strategy. Apart from traditional methods (patient reporting symptoms, body weight monitoring), novel home-care strategies allow guided adjustments in medical therapy through telemonitoring embedded in cardiac electronic implantable devices or through stand-alone diagnostic devices for hemodynamic monitoring. Wireless pulmonary artery pressure monitoring seems to reduce re-admission risk and is currently approved for this purpose in patients with heart failure. Multiparameter monitoring is also appealing and could be a valuable tool in managing these patients. However, invasive techniques face several safety concerns and cost-effectiveness issues. Therefore, quest for future research and emerging technologies is necessary.

Right ventricular outflow tract high-density endocardial unipolar voltage mapping in patients with Brugada syndrome: evidence for electroanatomical abnormalities.

Aims: Epicardial structural abnormalities at the right ventricular outflow tract (RVOT) may provide the arrhythmia substrate in Brugada syndrome (BrS). Electroanatomical endocardial unipolar voltage mapping is an emerging tool that accurately identifies epicardial abnormalities in different clinical settings. This study investigated whether endocardial unipolar voltage mapping of the RVOT detects electroanatomical abnormalities in patients with BrS. Methods and results: Ten asymptomatic patients (8 males, 34.5 ± 11.2 years) with spontaneous type 1 ECG pattern of BrS and negative late gadolinium enhancement-cardiac magnetic resonance imaging (LGE-c-MRI) underwent high-density endocardial electroanatomical mapping (>800 points). Using a cut-off of 1 mV and 4 mV for normal bipolar and unipolar voltage, respectively, derived from 20 control patients without structural heart disease established by LGE-c-MRI, the extend of low-voltage areas within the RVOT was estimated using a specific calculation software. The mean RVOT area presenting low-voltage bipolar signals in BrS patients was 3.4 ± 1.7 cm2 (range 1.5-7 cm2). A significantly greater area of abnormal unipolar signals was identified (12.6 ± 4.6 cm2 [range 7-22 cm2], P: 0.001). Both bipolar and unipolar electroanatomical abnormalities were mainly located at the free wall of the RVOT. The mean RVOT activation time was significantly prolonged in BrS patients compared to control population (86.4 ± 16.5 vs. 63.4 ± 9.7 ms, P < 0.001). Isochronal mapping demonstrated lines of conduction slowing within the RVOT in 8/10 BrS patients. Conclusion: Wide areas of endocardial unipolar voltage abnormalities that possibly reflect epicardial structural abnormalities are identified at the RVOT of BrS patients.

Low-voltage areas detected by high-density electroanatomical mapping predict recurrence after ablation for paroxysmal atrial fibrillation.

INTRODUCTION: We aimed to evaluate the extent of atrial fibrosis in paroxysmal atrial fibrillation (AF) and the correlation with ablation outcomes after pulmonary vein antral isolation (PVΑI) using a mapping system with high-resolution and high-spatial sampling. METHODS AND RESULTS: We prospectively enrolled 80 consecutive patients (45 males, median age 60.26 years) with symptomatic paroxysmal AF who were scheduled for PVAI. Prior to PVAI, high-density bipolar voltage mapping (median number of 2,485 points) was carried out during sinus rhythm in all patients. Criteria for an adequate left atrium (LA) shell were > 2,000 points. Each acquired point was classified according to the peak-to-peak bipolar voltage electrogram based on two criteria (criterion A: healthy > 0.8 mV, border zone: 0.4-0.8 mV and scarred: < 0.4 mV, criterion Β: healthy: > 0.5 mV, border zone: 0.25-0.5 mV and scarred: < 0.25 mV). The extent of low-voltage area < 0.4 mV significantly predicted atrial tachyarrhythmia recurrence after the blanking period (P = 0.002). In univariate analysis, the presence of LA voltage areas < 0.4 mV more than 10% of the total surface area was the only significant predictor of arrhythmia recurrence. The analysis based on window B cutoff values failed to demonstrate any predictors of arrhythmia recurrence. CONCLUSION: These data demonstrate that the existence of LA voltage areas < 0.4 mV more than 10% of the total LA surface area predicts arrhythmia recurrence following PVAI for paroxysmal AF.

Medical Treatment in Heart Failure with Reduced Ejection Fraction: A Proposed Algorithm Based on the Patient's Electrolytes and Congestion Status.

In heart failure (HF) with reduced ejection fraction (HFrEF), four classes of drugs (ß-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor neprilysin inhibitors, mineralocorticoid receptor antagonists, and the most recent Sodium-Glucose Co-Transporters 2 Inhibitors) have demonstrated positive results in randomized controlled trials (RCTs). Nevertheless, the latest RCTs are not proper for comparison since they were carried out at various times with dissimilar background therapies and the patients enrolled did not have the same characteristics. The difficulty of extrapolating from these trials and proposing a common framework appropriate for all cases is thus obvious. Despite the fact that these four agents are now the fundamental pillars of HFrEF treatment, the built-up algorithm of initiation and titration is a matter of debate. Electrolyte disturbances are common in HFrEF patients and can be attributed to several factors, such as the use of diuretics, renal impairment, and neurohormonal activation. We have identified several HFrEF phenotypes according to their sodium (Na+) and potassium (K+) status in a "real world" setting and suggest an algorithm on how to introduce the most appropriate drug and set up therapy based on the patients' electrolytes and the existence of congestion.

A New Hope: Sodium-Glucose Cotransporter-2 Inhibition to Prevent Atrial Fibrillation.

Atrial arrhythmias are common in patients with diabetes mellitus (DM), and despite recent advances in pharmaceutical and invasive treatments, atrial fibrillation (AF) and atrial flutter (AFl) are still associated with substantial mortality and morbidity. Clinical trial data imply a protective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on the occurrence of AF and AFl. This review summarizes the state of knowledge regarding DM-mediated mechanisms responsible for AF genesis and recurrence but also discusses the recent data from experimental studies, published trials and metanalyses.

Reshaping Treatment of Heart Failure with Preserved Ejection Fraction.

Current data indicate that in the community, approximately 50% of patients with heart failure (HF) have preserved left ventricular (LV) ejection fraction (LVEF)­the so-called HFpEF. Treatment of HFpEF has been considered an unmet need for decades. We believe that the main underlying reasons have been (a) the ever-changing LVEF cut-offs used for HF classification; (b) controversies regarding the definition of the LVEF normal range; (c) the fact that HFpEF does not represent a phenotype, but a category of diseases with entirely different characteristics (hypertensive heart disease, valvular heart disease (VHD), hypertrophic cardiomyopathy (HCM) etc.); (d) the lack of recognition that hypertensive HFpEF is the most common and important HFpEF phenotype; (e) the assumption that neurohormonal overactivity is absent in HF patients with a LVEF > 45−50% which has been proven to be wrong. Current HFpEF trials, in which the vast majority of the participants suffered from hypertension (HTN), whereas VHD and HCM were absent, demonstrated that neurohormonal and sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective in HF patients over a wide LVEF range. Thus, restricting these lifesaving treatments to HF patients with reduced LVEF is not justified anymore and it should be additionally considered for HFpEF patients suffering from HTN.

Safety, long-term outcomes and predictors of recurrence following a single catheter ablation procedure for atrial fibrillation.

Background: Data regarding long-term outcomes of atrial fibrillation (AF) catheter ablation are limited. This study evaluated the safety, long-term efficacy and predictors of recurrence after a single left atrial ablation procedure in patients with paroxysmal (PAF) and non-paroxysmal AF (NPAF). Methods: Data from 520 patients (354 males, mean age 57.08 ± 11.33 years) with PAF (n = 356, 68.5%) or NPAF (n = 164, 31.5%) who underwent a single radiofrequency ablation procedure were analysed. Across the NPAF group, there were 143 (27.5%) patients with persistent AF and 21 (4%) with long-standing persistent AF. The mean follow-up period was 39.05 ± 20.83 months (range 19-60 months). Results: Arrhythmia recurrence was observed in 102/356 (28.7%) of PAF patients and in 63/164 (38.4%) of NPAF patients. In patient with PAF, sinus rhythm maintenance was observed in 76.9%, 73% and 71.3% of patients at 1, 2 and 5 years of follow-up, respectively. In patients with NPAF, sinus rhythm was maintained in 68.7%, 63.4% and 61.6% of patients at 1, 2 and 5 years of follow-up, respectively. Independent predictors of AF recurrence were left atrial diameter (OR 1.15, 95% CI 1.10-1.21, p < 0.01) as well as early arrhythmia recurrence during the blanking period of 3 months after the procedure (OR 8.13, 95% CI 5.10-12.82, p < 0.01). Major complications were observed in 11 patients (2.1%). Conclusions: Long-term arrhythmia-free survival rates remain high among PAF and NPAF patients after a single catheter ablation procedure. Left atrial diameter and early arrhythmia recurrence were independent predictors of late arrhythmia recurrence in both PAF and NPAF patients.

Predictors of Adverse Outcomes in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy: A Meta-Analysis of Observational Studies.

Arrhythmogenic cardiomyopathy (AC) is a hereditary disorder characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle. Our study aimed to systematically evaluate the impact of significant demographic, clinical, electrocardiographic, and echocardiographic factors in arrhythmic events in AC patients. MEDLINE and Cochrane library databases were manually searched without year or language restriction or any other limits until July 31, 2017. A pooled odds ratio with 95% confidence intervals was calculated for each of the risk factors. Our search retrieved 26 studies (n = 2680 patients, mean age: 37.9 years old, males: 51.9%) which were included in the quantitative synthesis. The most reliable predicting factors/parameters are the following: (1) male gender, (2) presyncope, (3) left ventricular dysfunction, (4) T-wave inversions in inferior leads, (5) proband status, (6) late potentials, (7) syncope, (8) inducibility at electrophysiological study, (9) right ventricular dysfunction, (10) epsilon waves, and (11) premature ventricular contractions greater than 1000/24 h. On the contrary, family history of sudden cardiac death, palpitations, premature ventricular contractions greater than 500/24 h, and T-wave inversions in right precordial leads fail to determine the outcome in this meta-analysis. In conclusion, multiple risk factors have been associated with arrhythmic events in AC patients. However, larger studies are needed to discriminate those patients who will benefit from implantable cardioverter defibrillators.

Safety and efficacy of DOACs vs acenocoumarol in patients undergoing catheter ablation of atrial fibrillation.

BACKGROUND: Thromboembolic complications can be life-threatening during atrial fibrillation (AF) catheter ablation. The aim of our study was to evaluate the safety and efficacy of continuous treatment using direct oral anticoagulants (DOACs) as an alternative to uninterrupted acenocoumarol for periprocedural anticoagulation. HYPOTHESIS: Continuous treatment with DOACs has similar safety and efficacy compared to acenocoumarol. METHODS: We enrolled 474 patients (mean age, 58 years; 68.4% male) undergoing AF catheter ablation between June 2013 and December 2016. All patients were equally assigned to take acenocoumarol (group 1, 136 patients) or DOACs (group 2, 338 patients) for ≥2 months before the procedure. We compared thromboembolic and bleeding complications between the 2 groups. RESULTS: Our analysis showed no significant difference in major and minor complications between the 2 patient groups. Specifically, 3 of 136 patients (2.2%) using uninterrupted acenocoumarol had a major complication (1 patient [0.7%] had transient ischemic attack resolved 8 hours later, 1 [0.7%] had pericardial tamponade, and 1 [0.7%] had a subcapsular renal hematoma) and 2 patients (1.4%) had minor complications (1 [0.7%] pseudoaneurysm and 1 [0.7%] groin hematoma). In group 2, 1 of 338 patients (0.3%) had a major complication (transient ischemic attack). In the same group, 7 patients (2.1%) had a minor complication (1 patient [0.3%] presented with pseudoaneurysm, 4 [1.2%] with pericardial effusion <1 cm, 1 [0.3%] femoral arteriovenous fistula between the femoral artery and femoral vein, and 1 [0.7%] groin hematoma). CONCLUSIONS: DOACs and acenocoumarol have similar safety and effectiveness regarding thromboembolic complications prevention without increasing bleeding complications.

Adenosine-guided radiofrequency catheter ablation of atrial fibrillation: A meta-analysis of randomized control trials.

BACKGROUND: The prognostic significance of adenosine-mediated dormant pulmonary vein conduction, and whether such dormant conduction should be eliminated, remains controversial. We sought to perform a meta-analysis of data from eligible studies to delineate the prognostic impact of adenosine-guided radiofrequency catheter ablation of atrial fibrillation. METHODS: A systematic literature search was performed using online databases in order to identify relevant studies from January 2004 to September 2016. Ten studies [six observational and four randomized control trials (RCTs)] were included in the analysis. RESULTS: Five studies (two observational and three RCTs) compared the efficacy of adenosine-mediated elimination of dormant conduction versus no adenosine test. Overall, the adenosine-guided ablation strategy displayed better long-term outcomes as compared with no adenosine testing (RR 1.08, 95% CI 1.01-1.14, p=0.02; Heterogeneity: I2=42%, p: 0.14). The meta-analysis of only RCTs failed to show any differences between the two strategies (RR 1.03, 95% CI 0.96-1.11, p=0.37; Heterogeneity: I2 0%, p: 0.41). Eight studies (five observational and three RCTs) addressed the efficacy of adenosine-induced dormant conduction and additional ablation versus no dormant conduction during adenosine challenge. Overall, a trend towards a better outcome in those without dormant conduction during drug challenge was noted (RR 0.89, 95% CI 0.77-1.03, p=0.11; Heterogeneity: I2 65% p: 0.006). The pooled analysis of RCTs failed to show any differences between the two arms (RR 0.90, 95% CI 0.62-1.30, p= 0.57; Heterogeneity: I2 88%, p: 0.0002). CONCLUSIONS: Adenosine-guided radiofrequency catheter ablation of atrial fibrillation does not provide additional benefit in terms of freedom of arrhythmia recurrence.

Efficacy and safety of novel anticoagulants in the elderly.

Atrial fibrillation and venous thromboembolism (VTE) are common disorders associated with maleficent thrombotic events, particularly in the elderly patients. Polypharmacy, co-morbidities, and altered pharmacokinetics, often present in these patients, render the use of anticoagulants quite challenging. Novel oral anticoagulants (NOACs) have recently emerged as alternatives to Vitamin K Antagonists (VKAs) and are gradually increasing their popularity mainly because of their fewer drug and food interactions and ease of use. Their effectiveness and safety has been well-established in the general population but the balance between benefit and harm in the elderly is still unclear. Routine use in these patients is uncommon. Accumulating data have shown that the benefit of NOACs is consistent among all age groups, featuring equal or greater efficacy in preventing thrombotic events. Excess bleedings were lower with NOACs in comparison to VKAs, but bleeding patterns were disparate among them and head to head comparison is not available. The present review highlights on the efficacy and safety of novel anticoagulants in the elderly population.

Prediction of atrial fibrillation development and progression: Current perspectives.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Several conventional and novel predictors of AF development and progression (from paroxysmal to persistent and permanent types) have been reported. The most important predictor of AF progression is possibly the arrhythmia itself. The electrical, mechanical and structural remodeling determines the perpetuation of AF and the progression from paroxysmal to persistent and permanent forms. Common clinical scores such as the hypertension, age ≥ 75 years, transient ischemic attack or stroke, chronic obstructive pulmonary disease, and heart failure and the congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category scores as well as biomarkers related to inflammation may also add important information on this topic. There is now increasing evidence that even in patients with so-called lone or idiopathic AF, the arrhythmia is the manifestation of a structural atrial disease which has recently been defined and described as fibrotic atrial cardiomyopathy. Fibrosis results from a broad range of factors related to AF inducing pathologies such as cell stretch, neurohumoral activation, and oxidative stress. The extent of fibrosis as detected either by late gadolinium enhancement-magnetic resonance imaging or electroanatomic voltage mapping may guide the therapeutic approach based on the arrhythmia substrate. The knowledge of these risk factors may not only delay arrhythmia progression, but also reduce the arrhythmia burden in patients with first detected AF. The present review highlights on the conventional and novel risk factors of development and progression of AF.

Brugada Syndrome:Risk Stratification And Management.

The Brugada syndrome (BrS) is an arrhythmogenic disease associated with an increased risk of ventricular fibrillation and sudden cardiac death. The risk stratification and management of BrS patients, particularly of asymptomatic ones, still remains challenging. A previous history of aborted sudden cardiac death or arrhythmic syncope in the presence of spontaneous type 1 ECG pattern of BrS phenotype appear to be the most reliable predictors of future arrhythmic events. Several other ECG parameters have been proposed for risk stratification. Among these ECG markers, QRS-fragmentation appears very promising. Although the value of electrophysiological study still remains controversial, it appears to add important information on risk stratification, particularly when incorporated in multiparametric scores in combination with other known risk factors. The present review article provides an update on the pathophysiology, risk stratification and management of patients with BrS.

Catheter ablation of anteroseptal accessory pathways from the aortic cusps: A case series and a review of the literature.

Data regarding catheter ablation of anteroseptal accessory pathways through the aortic cusps are limited. We describe two cases of true para-Hisian accessory pathways successfully ablated from the aortic cusps (right coronary cusp and non-coronary cusp, respectively) along with a review of the current literature. Due to the close proximity to the atrioventricular node and the high risk of complication, mapping of the aortic cusps should always be considered in the case of anteroseptal accessory pathways. Anteroseptal accessory pathways can be safely and effectively ablated from the aortic cusps with good long-term outcomes.

Managing atrial fibrillation in the very elderly patient: challenges and solutions.

Atrial fibrillation (AF) is the most common arrhythmia affecting elderly patients. Management and treatment of AF in this rapidly growing population of older patients involve a comprehensive assessment that includes comorbidities, functional, and social status. The cornerstone in therapy of AF is thromboembolic protection. Anticoagulation therapy has evolved, using conventional or newer medications. Percutaneous left atrial appendage closure is a new invasive procedure evolving as an alternative to systematic anticoagulation therapy. Rate or rhythm control leads to relief in symptoms, fewer hospitalizations, and an improvement in quality of life. Invasive methods, such as catheter ablation, are the new frontier of treatment in maintaining an even sinus rhythm in this particular population.