Effect of 28-mm Cryoballoon Ablation on Major Atrial Ganglionated Plexi.

OBJECTIVES: The authors intended to investigate if 28-mm cryoballoon (CB) ablation also modifies the 4 major atrial ganglionaated plexi (GP). BACKGROUND: The major atrial GP facilitate the initiation and maintenance of atrial fibrillation (AF). The 28-mm CB covers a large surface area of the left atrium and probably the GP areas. METHODS: High-frequency stimulation (20 Hz) was delivered to the area of anterior right GP (ARGP), inferior right GP, superior left (SLGP), and inferior left GP (ILGP). Positive GP sites were defined as a prolongation of R-wave to R-wave (RR) interval during AF by >50%. The area of each GP before and after CB ablation was compared. RESULTS: A total of 18 patients with paroxysmal AF who underwent CB and radiofrequency ablation and had positive GP sites were reviewed. The Wilcoxon signed-rank test was used to assess the effects of CB ablation on each GP. There was a statistically significant difference in the area of all 4 GP after CB ablation: 1) ARGP area: 2.9 cm2 (interquartile range [IQR]: 2.1 to 3.5 cm2) pre-CB, 0.1 cm2 (IQR: 0 to 0.6 cm2) post-CB, p = 0.0002; 2) inferior right GP area: 2.1 cm2 (IQR: 0.9 to 2.9 cm2) pre-CB, 0.5 cm2 (IQR: 0 to 1.7 cm2) post-CB, p = 0.001; 3) SLGP area: 1.4 cm2 (IQR: 0.6 to 2.4 cm2) pre-CB, 0 cm2 (IQR: 0 to 0 cm2) post-CB, p = 0.0002; and 4) ILGP area: 1.3 cm2 (IQR: 0.3 to 2.2 cm2) pre-CB, 0.3 cm2 (IQR: 0 to 1.6 cm2) post-CB, p = 0.008. CONCLUSIONS: The surface area of all 4 of the major atrial GP was substantially reduced by CB ablation. The SLGP and ARGP had the largest, whereas the ILGP had the least percent of reduction following CB ablation. Part of the therapeutic effects of CB ablation may result from modifying the 4 major atrial GP.

Low-Level Vagus Nerve Stimulation Suppresses Post-Operative Atrial Fibrillation and Inflammation: A Randomized Study.

OBJECTIVES: This study sought to examine the efficacy of low-level vagus nerve stimulation (LLVNS) in suppressing post-operative atrial fibrillation (POAF) and inflammatory cytokines in patients undergoing cardiac surgery. BACKGROUND: POAF often complicates cardiac surgery. METHODS: Patients undergoing cardiac surgery were randomized to active or sham LLVNS. In all patients, a bipolar wire was sutured to the vagus nerve pre-ganglionic fibers alongside the lateral aspect of the superior vena cava. High-frequency (20 Hz) stimulation, 50% below the threshold for slowing the heart rate, was delivered for 72 h in the LLVNS group. The development of POAF was monitored continuously during the entire hospital stay by use of telemetry. Blood was collected on arrival in the intensive care unit and at 24 and 72 h for measurement of inflammatory cytokines. Patients were followed up within 1 month after cardiac surgery. RESULTS: A total of 54 patients were randomized to either active LLVNS (n = 26) or sham control (n = 28). The baseline characteristics of the patients were balanced in the 2 groups. POAF occurred in 3 patients (12%) in the LLVNS group and 10 patients (36%) in the control group (hazard ratio: 0.28; 95% confidence interval: 0.10 to 0.85; p = 0.027). None of the patients developed any complications as a result of wire placement. At 72 h, serum tumor necrosis factor-α and interleukin-6 levels were significantly lower in the LLVNS group than in the control group. CONCLUSIONS: These data suggest that LLVNS suppresses POAF and attenuates inflammation in patients undergoing cardiac surgery. Further studies are warranted.

Intermittent vs. Continuous Anticoagulation theRapy in patiEnts with Atrial Fibrillation (iCARE-AF): a randomized pilot study.

PURPOSE: We hypothesized that intermittent anticoagulation based on daily rhythm monitoring using the novel oral anticoagulants (NOACs) is feasible and safe among patients with paroxysmal atrial fibrillation (AF). METHODS: Patients with paroxysmal AF and ≥1 risk factors for stroke were randomized to either intermittent or continuous anticoagulation. Those in the intermittent group were instructed to transmit a daily ECG using an iPhone-based rhythm monitoring device. If AF was detected, patients received one of the NOACs for 48 h-1 week. Patients who failed to transmit an ECG for three consecutive days or more than 7 days total were crossed over to continuous anticoagulation. Patients in the continuous group received one of the NOACs. RESULTS: Fifty-eight patients were randomized to either intermittent (n = 29) or continuous anticoagulation (n = 29). Over a median follow-up of 20 months, 20 patients in the intermittent group failed to submit a daily ECG at least once (median three failed submissions). Four patients (14 %) crossed over to continuous anticoagulation due to failure to submit an ECG for three consecutive days. One stroke (continuous group) occurred during the study. Major bleeding occurred in two patients in the continuous and one patient in the intermittent group, after crossing over to continuous anticoagulation. In a prespecified per-protocol analysis, gastrointestinal bleeding was more frequent in the continuous group (16 vs. 0 %; p = 0.047). CONCLUSIONS: Intermittent anticoagulation based on daily rhythm monitoring is feasible and may decrease bleeding in low-risk patients with paroxysmal AF. A larger trial, adequately powered to detect clinical outcomes, is warranted.

Smartphone-based arrhythmia monitoring.

The use of smartphones for arrhythmia monitoring is another leap for ECG utilization and arrhythmia detection - effectively taking the technology to any smartphone user. Smart wearable technology, while very common, is limited mostly to activity tracking and exercise motivation. Rhythm strip generating smartphone products (Kardia Mobile by AliveCor and ECG Check by Cardiac Designs) are more powerful at arrhythmia detection than wearable monitors. These products, which have been studied in a variety of situations, rely on an external device with metal sensors to create a rhythm strip, which is usually Lead I. A different subset of smartphone products use photoplethysmography through a phone camera and light to detect atrial fibrillation. Together, these products are creating a paradigm shift in rhythm detection and monitoring.

Comparison of QT Interval Readings in Normal Sinus Rhythm Between a Smartphone Heart Monitor and a 12-Lead ECG for Healthy Volunteers and Inpatients Receiving Sotalol or Dofetilide.

INTRODUCTION: A variety of medications ranging from antiarrhythmics to psychotropics, as well as conditions such as bradycardia, can prolong the QT interval, increasing the risk for life-threatening arrhythmias. Monitoring the corrected QT interval (QTc) is therefore critical for patient safety. The recent development of smart phone heart monitors (SHM) may allow for easier QTc monitoring. We sought to evaluate the accuracy of an SHM for assessing the QTc, as compared to the standard 12-lead ECG. METHODS AND RESULTS: We compared the QTc interval in lead-I and lead-II between an SHM and 12-lead ECG. Healthy volunteers and hospitalized patients in sinus rhythm being loaded on dofetilide or sotalol were included. Manual and automatic measurements were studied. Across 99 healthy volunteers, the SHM QTc demonstrated good agreement (bias = 4 milliseconds, standard deviation of bias = 11 milliseconds) compared to the 12-lead ECG, using the Bland-Altman method of agreement. Across all hospitalized patients, the SHM was capable of demonstrating QTc prolongation. Between the 12-lead ECG and SHM, lead-I measurements had reasonable agreement (bias = 3 milliseconds, standard deviation of bias = 46 milliseconds). A QTc of > 500 milliseconds was associated with a higher likelihood (OR = 12.0; 95% CI 1.5-111.4; P = 0.02) to not achieve perfect agreement. CONCLUSION: The SHM is accurate in measuring QTc interval in sinus rhythm when compared to 12-lead ECG in healthy volunteers. For patients receiving QT prolonging antiarrhythmics, SHM is capable of detecting QTc prolongation, and lead-I of the SHM is most accurate in measuring the QTc if < 500 milliseconds.

Ablation of Ventricular Tachycardia in Patients with Ischemic Cardiomyopathy.

Ventricular tachycardias (VTs) occurring after prior myocardial infarction are usually caused by reentrant circuits formed by surviving myocardial bundles. Although part of the reentrant circuits may be located in the midmyocardium or epicardium, most of the VTs can be safely and successfully ablated by endocardial ablation targeting the late potentials/local abnormal ventricular activation, which are surrogates for the surviving myocardial bundles. A combination of activation, substrate, pace, and entrainment mapping, as well as the use of contact force catheters, further improves ablation success and safety.

The use of low-level electromagnetic fields to suppress atrial fibrillation.

BACKGROUND: Extremely low-level electromagnetic fields have been proposed to cause significant changes in neural networks. OBJECTIVE: We sought to investigate whether low-level electromagnetic fields can suppress atrial fibrillation (AF). METHODS: In 17 pentobarbital anesthetized dogs, bilateral thoracotomies allowed the placement of multielectrode catheters in both atria and at all pulmonary veins. AF was induced by rapid atrial pacing (RAP) or programmed atrial extrastimulation. At baseline and end of each hour of RAP, during sinus rhythm, atrial programmed stimulation gave both the effective refractory period (ERP) and the width of the window of vulnerability. The latter was a measure of AF inducibility. Microelectrodes inserted into the anterior right ganglionated plexi recorded neural firing. Helmholtz coils were powered by a function generator inducing an electromagnetic field (EMF; 0.034 µG, 0.952 Hz). The study sample was divided into 2 groups: group 1 (n = 7)-application of EMF to both cervical vagal trunks; group 2 (n = 10)-application of EMF across the chest so that the heart was located in the center of the coil. RESULTS: In group 1, EMF induced a progressive increase in AF threshold at all pulmonary vein and atrial sites (all P < .05). In group 2, the atrial ERP progressively shortened and ERP dispersion and window of vulnerability progressively increased (P < .05 compared to baseline values) during 3 hours of RAP and then returned to baseline values during 3 hours of combined application of RAP and EMF (P < .05 compared to the end of the third hour of RAP). The frequency and amplitude of the neural activity recorded from the anterior right ganglionated plexi were markedly suppressed by EMF in both groups. CONCLUSION: Pulsed EMF applied to the vagal trunks or noninvasively across the chest can significantly reverse AF inducibility.

Role of Atrio-Ventricular Junction Ablation in Symptomatic Atrial Fibrillation for Optimization of Cardiac Resynchronization Therapy.

Cardiac resynchronization (CRT) therapy is indicated in patients with at least mildly symptomatic heart failure, left ventricular ejection fraction ≤35% and wide QRS, and has been associated with decreased morbidity and mortality. Unfortunately, approximately 30% of the patients appropriately selected for therapy do not respond to CRT. Among the reasons for non-response, atrial fibrillation (AF) plays a prominent role. AF limits the degree of biventricular pacing during CRT, not only when the ventricular rate is fast and highly irregular, but also during periods of of relatively constant rate, by causing fusion and pseudo-fusion complexes. Importantly, achievement of nearly 100% biventricular pacing is necessary to derive benefit from CRT. A simple, albeit irreversible, method to maximize biventricular pacing in patients with AF who are otherwise eligible for CRT is atrioventricular junction (AVJ) ablation. In this review, we discuss the role of AVJ ablation in CRT optimization in patients with AF. The available evidence from observational non-randomized studies suggests that AVJ ablation in patients with AF qualifying for CRT may offer improvement in heart failure symptoms, better survival, and better cardiac function. In light of the inherent limitations of non-randomized studies, further randomized studies are needed to support this treatment option.

Cardiac resynchronization therapy after atrioventricular junction ablation for symptomatic atrial fibrillation: a meta-analysis.

AIMS: Atrioventricular junction (AVJ) ablation with permanent pacing improves symptoms in selected patients with atrial fibrillation (AF). The optimal pacing modality after AVJ ablation remains unclear. We performed a meta-analysis of randomized controlled trials to examine whether cardiac resynchronization therapy (CRT) is superior to right ventricular (RV) pacing in this patient population. METHODS AND RESULTS: We searched the MEDLINE and EMBASE databases for studies evaluating the effect of CRT vs. RV pacing after AVJ ablation for AF. Pooled risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were calculated for categorical and continuous outcomes, respectively, using a random effects model. Five trials involving 686 patients (413 in CRT and 273 in RV pacing group) were included in the analysis. On the basis of the pooled estimate across the studies, CRT resulted in a non-significant reduction in mortality (RR = 0.75, 95% CI 0.43-1.30; P= 0.30) and a significant reduction in hospitalizations for heart failure (RR = 0.38, 95% CI = 0.17-0.85; P= 0.02) compared with RV pacing. Cardiac resynchronization therapy did not improve 6 min walk distance (mean difference 15.7, 95% CI -7.2 to 38.5 m; P= 0.18) and Minnesota Living with Heart Failure quality-of-life score (mean difference -3.0, 95% CI -8.6 to 2.6; P= 0.30) compared with RV pacing. The change in left ventricular ejection fraction between baseline and 6 months favoured CRT (mean change 2.0%, 95% CI 1.5-2.4%; P< 0.001). CONCLUSION: Cardiac resynchronization therapy may be superior to RV pacing in patients undergoing AVJ ablation for AF. Further studies, adequately powered to detect clinical outcomes, are required.

Distinct roles for angiotensin-converting enzyme 2 and carboxypeptidase A in the processing of angiotensins within the murine heart.

Angiotensin-converting enzyme 2 (ACE2), a homologue of angiotensin-converting enzyme (ACE), converts angiotensin (Ang) I to Ang(1-9) and Ang II to Ang(1-7), but does not directly process Ang I to Ang II. Cardiac function is compromised in ACE2 null mice; however, the importance of ACE2 in the processing of angiotensin peptides within the murine heart is not known. We determined the metabolism of angiotensins in wild-type (WT), ACE (ACE(-/-)) and ACE2 null mice (ACE2(-/-)). Angiotensin II was converted almost exclusively to Ang(1-7) in the cardiac membranes of WT and ACE(-/-) strains, although generation of Ang(1-7) was greater in the ACE(-/-) mice (27.4 +/- 4.1 versus 17.5 +/- 3.2 nmol(-1) mg h(-1) for WT). The ACE2 inhibitor MLN4760 significantly attenuated Ang II metabolism and the subsequent formation of Ang(1-7) in both strains. In the ACE2(-/-) hearts, Ang II metabolism and the generation of Ang(1-7) were significantly attenuated; however, the ACE2 inhibitor reduced the residual Ang(1-7)-forming activity in this strain. Angiotensin I was primarily converted to Ang(1-9) (WT, 28.9 +/- 3.1 nmol(-1) mg h(-1); ACE(-/-), 49.8 +/- 5.3 nmol(-1) mg h(-1); and ACE2(-/-), 35.9 +/- 5.4 nmol(-1) mg h(-1)) and to smaller quantities of Ang(1-7) and Ang II. Although the ACE2 inhibitor had no effect on Ang(1-9) formation, the carboxypeptidase A inhibitor benzylsuccinate essentially abolished the formation of Ang(1-9) and increased the levels of Ang I in cardiac membranes. In conclusion, our studies in the murine heart suggest that ACE2 is the primary pathway for the metabolism of Ang II and the subsequent formation of Ang(1-7), a peptide that, in contrast to Ang II, exhibits both antifibrotic and antiproliferative actions.