Defining the blanking period, using continuous ECG monitoring, after cryoballoon pulmonary vein isolation.

BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. A blanking period (BP) of 3 months is used in clinical trials and practice. However, the optimal BP duration after PVI remains undefined. OBJECTIVE: The aim of this study was to objectively define, using continuous monitoring by an implantable loop recorder, the optimal BP duration after cryoballoon PVI. METHODS: We enrolled consecutive patients who had cryoballoon PVI and an implantable loop recorder. We determined the time of the last confirmed episode of AF within the blanking period. This was then correlated with AF recurrence in the first year after ablation. RESULTS: There were 210 patients (66 ± 9 years; 138 [66%] male; 116 [55%] paroxysmal AF; CHA2DS2-VASc score, 2.5 ± 1.6). We defined 4 distinct groups based on the last AF episode within the BP: no AF days 0-90 (n = 96 [46%]) and last AF 0-30 days (n = 46 [22%]), 31-60 days (n = 18 [9%]), and 61-90 days (n = 50 [24%]). After the 3-month BP, 101 (48%) patients had AF recurrence at 160 ± 86 days. Compared with patients with no AF in the BP, those with recurrent AF and AF burden >0% 30 days after ablation had a significantly greater AF recurrence during long-term follow-up (P = .001). CONCLUSION: Our data show that the approximately one-third of patients in whom AF occurs and who have a burden of >0% after the first month that follows PVI are at significantly higher risk of long-term recurrent AF. We therefore suggest that the blanking period be limited to a month after cryoballoon PVI.

Incidence and Predictors of Very Late Recurrence of Atrial Fibrillation Following Cryoballoon Pulmonary Vein Isolation.

BACKGROUND: A very late recurrence (VLR) of atrial fibrillation (AF) is considered present when the first recurrence of AF occurs ≥12 months following ablation. Prior studies characterizing VLR have not used an implantable loop recorder for ECG monitoring. Thus, it is unknown whether VLR truly occurs or whether these patients have simply had unrecognized AF. Our objective was to assess the incidence and predictors of VLR in patients who underwent cryoballoon pulmonary vein isolation alone, had an implantable loop recorder, and were confirmed AF free for at least 1 year. METHODS: We enrolled consecutive patients with paroxysmal or persistent AF who underwent cryoballoon pulmonary vein isolation and had an implantable loop recorder implanted <3 months post-ablation. Patients free of AF 1 year post-ablation were followed prospectively for recurrent AF. All AF episodes were adjudicated. RESULTS: We included 188 patients (66±10 years; 116 [62%] men; 102 [54%] paroxysmal AF; CHA2DS2-VASc, 2.6±1.7). After 1 year post-pulmonary vein isolation, 93 (49%) patients remained AF free. During subsequent follow-up, 30 (32%) patients had VLR of AF. The only independent risk factor for VLR was an elevated CHA2DS2-VASc score (hazard ratio, 1.317 [95% CI, 1.033-1.6979]; P=0.026). Patients with CHA2DS2-VASc score ≥4 represented a quarter of the population and were at the highest risk. CONCLUSIONS: Our data using implantable loop recorders for continuous ECG monitoring post-AF ablation show that VLR occurs in a third of patients after an apparently successful cryoballoon pulmonary vein isolation procedure. Additional strategies are needed to ensure long-term freedom from AF recurrences in these high-risk patients.

Incidence, duration, pattern, and burden of de novo atrial arrhythmias detected by continuous ECG monitoring using an implantable loop recorder following ablation of the cavotricuspid isthmus.

Background: Following cavotricuspid isthmus (CTI) ablation, many patients with atrial flutter (AFL) are diagnosed with atrial fibrillation (AF). The incidence, duration, pattern, and burden of AF remain undefined. These may have implications for the management of these patients. Objective: To classify the incidence, duration, pattern, and burden of AF/AFL using an implantable loop recorder (ILR) after CTI ablation. Methods: We enrolled consecutive patients with CTI-dependent AFL, no known history of AF, and CHA2DS2-VASc ≥ 2. An ILR was implanted before or within 90 days of ablation. The time to first AF/AFL, pattern, duration, and burden of longest AF/AFL were determined. Five distinct AF/AFL cohorts were identified: no AF/AFL and those with recurrences of isolated, clustered, frequent, or persistent AF/AFL. Results: Fifty-two patients (81% male; 73 ± 9 years; CHA2DS2-VASc 3.7 ± 1.2) were followed for 784 (interquartile range [IQR] 263, 1150) days. AF/AFL occurred in 44 (85%) patients at 64 (IQR 8, 189) days post-CTI ablation and was paroxysmal in 31 (70%) patients (burden 0.6% [IQR 0.1, 4.8]). AF/AFL was isolated (n = 5, 11%), clustered (n =7, 16%), frequent (n =19, 43%), and persistent (n =13, 30%). The longest AF episode was <24 hours in 27 (61%) patients. Conclusion: Following CTI ablation in AFL patients, although AF/AFL occurs in most patients, the burden is low and episodes were <24 hours in the majority of patients. Additional studies are needed to determine whether long-term electrocardiographic monitoring can help guide management of patients undergoing CTI ablation.

Detection of atrial fibrillation using an implantable loop recorder following cryptogenic stroke: implications for post-stroke electrocardiographic monitoring.

PURPOSE: Approximately 10-40% of strokes are cryptogenic (CS). Long-term electrocardiographic (ECG) monitoring has been recommended in these patients to search for atrial fibrillation (AF). An unresolved issue is whether ambulatory ECG (AECG) monitoring should be performed first, followed by an implantable loop recorder (ILR) if AECG monitoring is non-diagnostic, or whether long-term ECG monitoring should be initiated using ILRs from the onset. The purpose of this study was to assess, using an ILR, AF incidence in the first month after CS. METHODS: We enrolled consecutive CS patients referred for an ILR. All patients were monitored via in-hospital continuous telemetry from admission until the ILR (Medtronic [Minneapolis, MN] LINQ™) was implanted. The duration and overall burden of all AF episodes ≥ 2 min was determined. RESULTS: The cohort included 343 patients (68 ± 11 years, CHA2DS2-VASc 3.5 ± 1.7). The time between stroke and ILR was 3.7 ± 1.5 days. During the first 30 days, only 18 (5%) patients had AF. All episodes were paroxysmal, lasting from 2 min to 67 h and 24 min. The median AF burden was 0.85% (IQR 0.52, 10.75). During 1 year of follow-up, 67 (21%) patients had AF. CONCLUSION: The likelihood of AF detection by an ILR in the first month post-CS is low. Thus, the diagnostic yield of 30 days of AECG monitoring is likely to be limited. These data suggest a rationale for proceeding directly to ILR implantation prior to hospital discharge in CS patients, as many have AF detected during longer follow-up.

The Efficacy of His Bundle Pacing: Lessons Learned From Implementation for the First Time at an Experienced Electrophysiology Center.

OBJECTIVES: This study sought to evaluate the clinical and procedural characteristics impacting outcomes during implementation of a His bundle pacing (HBP) program in a real-world setting. BACKGROUND: Right ventricular pacing is associated with an elevated risk of heart failure, but device reprogramming and upgrades have significant challenges. HBP has emerged as an alternative and is reported to be highly successful in the hands of highly experienced centers. METHODS: All patients referred for permanent pacemaker implantation at the Valley Hospital (Ridgewood, New Jersey) between October 2015 and October 2017 were evaluated; a subset of 24% was selected for HBP. RESULTS: Permanent HBP was feasible with an acute implant success rate of 75%. HBP in the presence of bundle branch block (64% vs. 85%; p = 0.05) or complete heart block (56% vs. 83%; p = 0.03) was significantly less successful. The pattern of atrioventricular block in combination with bundle branch block (BBB) further affects outcomes. HBP is highly successful across the spectrum of atrioventricular block pattern severity in the absence of BBB. In the presence of BBB, Mobitz II AV block and complete heart block significantly attenuated HBP success compared with Mobitz I atrioventricular block (62% vs. 100%; p = 0.02). A rising threshold was observed in 30%, and 8% required lead intervention. CONCLUSIONS: HBP was feasible and readily learned with a high implant success in the hands of experienced electrophysiologists without prior exposure to the technique. BBB and atrioventricular block pattern appears to affect success. The technique is limited by a high rate of rising thresholds and lead intervention. These data have important implications for patient selection.

Increased healthcare utilization associated with complete atrioventricular block in pacemaker patients.

PURPOSE: The purpose of the current study is to characterize and quantify the impact of complete atrioventricular block (cAVB) on heart failure hospitalization (HFH) and healthcare utilization in pacemaker (PM) patients. METHODS: Patients ≥ 18 years implanted with a dual-chamber PM from April 2008 to March 2014 were selected from the MarketScan® Commercial and Medicare Supplemental claims databases. Patients with ≤ 1-year continuous MarketScan enrollment prior to and post-implant, and those with prior HF diagnosis were excluded. Patients were dichotomized into those with cAVB, defined as a 3rd degree AVB diagnosis or AV node ablation in the year prior to PM implant, versus those without any AVB (noAVB). Post-implant HFH and associated costs were compared based on inpatient claims. RESULTS: The study cohort included 21,202 patients, of which 14,208 had no AVB and 6994 had cAVB, followed for 2.39 and 2.27 years, respectively. Patients with cAVB were associated with a significantly increased risk of cumulative HFH (HR 1.59 [95% CI 1.35-1.86] p < 0.001) and significantly higher costs ($636 [609-697] vs $369 [353-405] per pt-year, p < 0.001) compared to those with no AVB. CONCLUSIONS: Among dual-chamber PM patients without prior HF, cAVB is associated with a significantly increased risk of HFH and greater HF-related healthcare utilization. Identifying patients at high risk for HF in the setting of RV pacing, and potentially earlier use of biventricular or selective conduction system pacing, may reduce HF-related healthcare utilization.

Implantable Loop Recorders for Cryptogenic Stroke (Plus Real-World Atrial Fibrillation Detection Rate with Implantable Loop Recorders).

Cryptogenic stroke (CS) represents 10%-40% of ischemic strokes and is associated with significant morbidity and mortality and high risk of recurrence. Undetected atrial fibrillation is an important consideration in these patients. Tools for electrocardiographic monitoring range from 12-lead electrocardiogram to implantable loop recorders (ILRs). ILRs have become an important tool for long-term electrocardiogram monitoring in CS patients. Advancements in ILR technology are needed to ensure more robust connectivity and to help triage incoming data. An unresolved issue is what duration of AF indicates that the CS patient is at high risk for recurrent stroke and thus would benefit from initiation of anticoagulation.

Clinical Outcomes After Ablation of the AV Junction in Patients With Atrial Fibrillation: Impact of Cardiac Resynchronization Therapy.

BACKGROUND: Patients with atrial fibrillation (AF) often undergo AV junction ablation (AVJA) and pacemaker implantation. Right ventricular (RV) pacing contributes to increased risk of heart failure (HF), which may be mitigated by biventricular pacing. We sought to determine the impact of AVJA concurrent with RV versus biventricular pacemaker implantation on AF and HF hospitalizations. METHODS AND RESULTS: The MarketScan Commercial and Medicare Supplemental claims database was used to select 18- to 100-year-old patients with AF with pacemaker implantation. Patients were divided into those with an RV and a biventricular pacemaker and further into those who did (AVJA+) or did not undergo concurrent ablation. Separately, the AVJA+ group was divided into those receiving RV versus biventricular pacemakers. AF and HF hospitalization rates were compared between groups after matching on demographics, comorbidities, and baseline hospitalization rates. The study included 24 361 patients, with RV (n=23 377) or biventricular (n=984) pacemakers; 1611 patients underwent AVJA. AVJA+ was associated with reduced AF hospitalization risk (RV hazard ratio [HR], 0.31; P<0.001; biventricular HR, 0.20; P=0.003) compared with no AVJA. However, HF hospitalization risk was increased for RV (HR, 1.63; P=0.001), but not biventricular (HR, 0.98; P=0.942), pacemakers. In AVJA+ patients, biventricular pacing was associated with reduced risk of HF hospitalization versus RV pacing (HR, 0.62; P=0.017). CONCLUSIONS: In a large cohort of patients with AF, AVJA+ significantly reduced AF hospitalizations, irrespective of whether an RV or a biventricular pacemaker was implanted. However, AVJA was associated with a marked HF hospitalization increase in patients with an RV pacemaker, which was ameliorated with biventricular pacing.

Incidence and Time Course for Developing Heart Failure With High-Burden Right Ventricular Pacing.

BACKGROUND: Although right ventricular pacing can contribute to cardiomyopathy, the impact of complete atrioventricular block (cAVB) on heart failure (HF) development in pacemaker patients has not been well characterized. We evaluated the incidence and time course for developing HF after pacemaker implantation for cAVB. METHODS AND RESULTS: A MarketScan database identified patients undergoing dual-chamber pacemaker implantation from 2008 to 2014. Patients with cAVB were identified by an atrioventricular node ablation or diagnosis of third-degree AVB. Patients with ≥1 year of continuous MarketScan enrollment before and after implant and without a previous diagnosis of HF were dichotomized into those with cAVB and without AVB. The primary end point was new HF assessed over acute (0-6 months) and chronic (6 months to 4 years) phases post-pacemaker implantation. The cohort included 6994 cAVB patients and 14 208 patients without AVB, followed for 2.35 years (interquartile range, 1.62-3.39 years). After adjustment for baseline covariates, patients with cAVB experienced an increased risk of new-onset HF in the acute phase (hazard ratio, 1.62; 95% confidence interval, 1.48-1.79; P<0.001). Although the risk of HF remained elevated among those with cAVB in the chronic phase, the effect was attenuated (hazard ratio, 1.16; 95% confidence interval, 1.08-1.25; P<0.001). After pacemaker implantation, younger patients (≤55 years of age) and those with an antecedent history of atrial fibrillation experienced the highest risk of HF associated with cAVB. CONCLUSIONS: Patients with a diagnosis of cAVB, and thus presumed to have a higher burden of right ventricular pacing, experienced an increased risk of new-onset HF after pacemaker implantation compared with those without AVB. Better tools are needed to identify patients at high risk of developing HF in the setting of right ventricular pacing and to determine whether these patients benefit from upfront biventricular pacing.

Comparison of endovascular versus epicardial lead placement for resynchronization therapy.

Cardiac resynchronization therapy (CRT) has been shown to improve survival and symptoms in patients with severe left ventricular (LV) dysfunction, congestive heart failure, and prolonged QRS duration. LV lead placement is achieved by placing the lead in the coronary sinus, an endovascular approach, or by a minimally invasive robotic-assisted thoracoscopic epicardial approach. There are no data directly comparing the 2 methods. Patients eligible for CRT were randomized to the endovascular and epicardial arms. Coronary sinus lead placement was achieved using the standard technique, and epicardial leads were placed using a minimally invasive robotic-assisted thoracoscopic approach. The primary end point was a decrease in LV end-systolic volume index at 6 months. The secondary end points included 30-day mortality rate, measures of clinical improvement, 1-year electrical lead performance, and 1-year survival rate. The relative improvement of LV end-systolic volume index from baseline to 6 months was similar between the arms (28.8% for the transvenous [n = 12] vs 30.5% for the epicardial (n = 9) arm, p = 0.93). There were no significant differences in the secondary end points between the 2 groups. In conclusion, there were no differences in echocardiographic and clinical outcomes comparing a conventional endovascular approach versus robotic-assisted surgical epicardial LV lead placement for CRT in patients with heart failure. Surgical approaches are still a viable alternative when a transvenous procedure has failed or is not technically feasible.

Correlation of QT interval correction methods during atrial fibrillation and sinus rhythm.

The calculation of the corrected QT interval (QTc) is particularly problematic in patients during atrial fibrillation (AF). The aims of this study were to compare the QTc calculated using Bazett's formula in AF and sinus rhythm (SR) and determine whether alternative methods for QT correction were superior to Bazett's, in an effort to define the optimal method for QT correction in patients with AF. We evaluated consecutive patients with persistent AF admitted for initiation of dofetilide. The QT interval was corrected according to the following formulas: Bazett's, Fridericia, and Framingham. We compared the QTc interval on the last electrocardiogram in AF to the first electrocardiogram in SR. The cohort included 54 patients (age 60 ± 10 years, 80% men) with persistent AF for a median of 36 months. Bazett's overestimated QTc during AF compared with SR (464 ± 34 vs 445 ± 38 ms, p = 0.008); in contrast, Framingham underestimated it (385 ± 48 vs 431 ± 40 ms, p <0.001, respectively). However, there was no significant difference between the QTc interval in AF and SR when assessed by Fridericia (435 ± 33 vs 440 ± 35 ms, p = 0.46). There were 24 dofetilide dose reductions based on Bazett's QTc; this would have been avoided in 33% of patients had Fridericia been used. In conclusion, the commonly used Bazett's formula leads to an overestimation of the QTc during AF. This may result in unnecessary reduction in antiarrhythmic doses and thus drug efficacy. These data suggest that the Fridericia most closely approximates the QTc during AF to QTc during SR.

PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity.

Noonan syndrome (NS) is a developmental disorder characterized by facial dysmorphia, short stature, cardiac defects, and skeletal malformations. We recently demonstrated that mutations in PTPN11, the gene encoding the non-receptor-type protein tyrosine phosphatase SHP-2 (src homology region 2-domain phosphatase-2), cause NS, accounting for approximately 50% of cases of this genetically heterogeneous disorder in a small cohort. All mutations were missense changes and clustered at the interacting portions of the amino-terminal src-homology 2 (N-SH2) and protein tyrosine phosphatase (PTP) domains. A gain of function was postulated as a mechanism for the disease. Here, we report the spectrum and distribution of PTPN11 mutations in a large, well-characterized cohort with NS. Mutations were found in 54 of 119 (45%) unrelated individuals with sporadic or familial NS. There was a significantly higher prevalence of mutations among familial cases than among sporadic ones. All defects were missense, and several were recurrent. The vast majority of mutations altered amino acid residues located in or around the interacting surfaces of the N-SH2 and PTP domains, but defects also affected residues in the C-SH2 domain, as well as in the peptide linking the N-SH2 and C-SH2 domains. Genotype-phenotype analysis revealed that pulmonic stenosis was more prevalent among the group of subjects with NS who had PTPN11 mutations than it was in the group without them (70.6% vs. 46.2%; P<.01), whereas hypertrophic cardiomyopathy was less prevalent among those with PTPN11 mutations (5.9% vs. 26.2%; P<.005). The prevalence of other congenital heart malformations, short stature, pectus deformity, cryptorchidism, and developmental delay did not differ between the two groups. A PTPN11 mutation was identified in a family inheriting Noonan-like/multiple giant-cell lesion syndrome, extending the phenotypic range of disease associated with this gene.