Background: Repolarization alternans, defined as period-2 oscillation in the repolarization phase of the action potentials, provides a mechanistic link between cellular dynamics and ventricular fibrillation (VF). Theoretically, higher-order periodicities (e.g., periods 4, 6, 8,...) are expected but have minimal experimental evidence. Methods: We studied explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Optical mapping of the transmembrane potential was performed after staining the hearts with voltage-sensitive fluorescent dyes. Hearts were stimulated at an increasing rate until VF was induced. Signals recorded from the right ventricle endocardial surface prior to induction of VF and in the presence of 1:1 conduction were processed using the Principal Component Analysis and a combinatorial algorithm to detect and quantify higher-order dynamics. Results were correlated to the underlying electrophysiological characteristics as quantified by restitution curves and conduction velocity. Results: A prominent and statistically significant global 1:4 peak (corresponding to period-4 dynamics) was seen in three of the six studied hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel. Discussion: We present evidence of higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex-vivo human hearts. We infer from the independence of the period to the underlying restitution properties that the oscillation of the excitation-contraction coupling and calcium cycling mechanisms is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability that can degenerate into chaotic fibrillation and may provide targets for substrate-based ablation of VF.

Background: Infection is a well-recognized complication of cardiovascular implantable electronic device (CIED) implantation, including the more recently available subcutaneous implantable cardioverter-defibrillator (S-ICD). Although the AHA/ACC/HRS guidelines include recommendations for S-ICD use, currently there are no clinical trial data that address the diagnosis and management of S-ICD infections. Therefore, an expert panel was convened to develop consensus on these topics. Methods: A process mapping methodology was used to achieve a primary goal – the development of consensus on the diagnosis and management of S-ICD infections. Two face-to-face meetings of panel experts were conducted to recommend useful information to clinicians in individual patient management of S-ICD infections. Results: Panel consensus of a stepwise approach in the diagnosis and management was developed to provide guidance in individual patient management. Conclusion: Achieving expert panel consensus by process mapping methodology in S-ICD infection diagnosis and management was attainable, and the results should be helpful in individual patient management.

Background-—The incidence of cancer treatment–induced arrhythmia (CTIA) associated with novel, targeted chemotherapeutic agents (TCAs) has not been well described. Methods and Results-—We identified all patients treated at our institution from January 2010 to December 2015 with selected TCAs. We defined CTIA as any new arrhythmia diagnosis code within 6 months after treatment initiation. As a comparison, we also identified patients treated with anthracycline chemotherapy during the same period. We identified 5026 patients, of whom 2951 (58.7%) received TCAs and 2075 (41.3%) received anthracycline chemotherapy. In the overall cohort, 601 patients (12.0%) developed CTIA. Patients with CTIA were significantly older and more likely to have hypertension, diabetes mellitus, congestive heart failure, coronary disease, and sleep apnea. The incidence of CTIA at 6 months was significantly lower in the TCA group (9.3% versus 15.8%; P<0.001). In multivariate analysis, a history of hypertension (hazard ratio, 1.63; 95% confidence interval, 1.34–1.98), congestive heart failure (hazard ratio, 2.12; 95% confidence interval, 1.78–2.68), and male sex (hazard ratio, 1.25; 95% confidence interval, 1.06–1.47) were associated with a significantly increased risk of CTIA, whereas treatment with TCAs, compared with anthracycline chemotherapy, was associated with a significantly lower risk (hazard ratio, 0.60; 95% confidence interval, 0.51– 0.71). Conclusions-—Compared with anthracyclines, treatment with TCAs was associated with an ≈40% reduced risk of new-onset arrhythmia diagnoses during the first 6 months of treatment.

Background: T wave oversensing (TWOS) is a major drawback of the subcutaneous implantable cardioverter defibrillator (S-ICD). Data on predictors of TWOS in S-ICD recipients are limited. We sought to investigate predictors of TWOS in a cohort of patients receiving an S-ICD at our institution. Methods: S-ICD recipients at our center were identified retrospectively and stratified based on the presence or absence of TWOS. Clinical and electrocardiographic parameters were collected and compared between the 2 groups. Results: Ninety-two patients underwent an S-ICD implantation at our institution between April 2010 and January 2015. Six (6.5%) patients had TWOS. These patients were younger (38.1±13.7 vs. 52.3±16.1 years, p=0.04) and had higher left ventricle ejection fractions (48.5±14.9% vs. 28.4±12.2%, p<0.01) than patients without a history of TWOS. Baseline 12-lead electrocardiogram (ECG) parameters were not different between the 2 groups. Leads I, II, and avF (which mimic the sensing vectors of the S-ICD) were further inspected to identify ECG characteristics that could predict TWOS. The QRS amplitude in ECG lead I was significantly smaller in the TWOS group than in the non-TWOS group (3.7 vs. 7.4 mV, p=0.02). Conclusion: In this study, younger age, higher ejection fraction, and lower QRS amplitude were associated with TWOS. These findings could help identify patients referred for S-ICD at high-risk of TWOS.

Background: There is heightened interest in how real-world data (RWD) can be used to supplement or replace traditional mechanisms for collecting clinical information. A critical component in evaluating utility of RWD is assessing the validity and reliability of event measurement. Only two studies have validated Medicare claims with physician-adjudicated data collected in a clinical study and none in the pacemaker patient population. This study compares events identified in physician-adjudicated clinical registry data collected in the Micra Post-Approval Registry (PAR) with events identified via Medicare administrative claims in the Micra Coverage with Evidence (CED) Study. Methods: Patients who were dually enrolled in the Micra CED and the Micra PAR between March 9, 2017 and December 1, 2017 were included in the validation analysis. All patients intended to be implanted with a Micra device were eligible for participation in the Micra PAR. All Medicare fee-for-service beneficiaries implanted with a Micra device who met the 12-month continuous enrollment criteria were included in the Micra CED. We compared the count of acute (30-day) complications identified in the Medicare claims and the physician-adjudicated PAR data to assess agreement between data sources. Results: There were 230 patients dually enrolled in the Micra CED and Micra PAR studies during the study period. Overall, there were 17 acute events reported in either the Micra CED or the Micra PAR, with 95% agreement in the identification of events and absence of events between studies. Study disagreement between events reported in either study varied: arteriovenous fistula (50%), pulmonary embolism (67%), hemorrhage/hematoma (75%), and deep vein thrombosis (100%). Among physician-adjudicated events, there was no disagreement between the Micra CED and Micra PAR studies in any event type. Conclusion: Findings from this study demonstrate high agreement in event identification between Medicare claims data and registries for patients implanted with Micra leadless pacemakers.

Over one million cardiac pacemakers are implanted every year worldwide,[1] of which approximately 200,000 are implanted in the United States alone.[2] Combined with an aging population and increasing pacing indications, these numbers are expected to grow. Since the first pacemaker implantation in 1950s, cardiac pacemaker technology has rapidly advanced. Reduction in generator size, increased battery longevity, quality of pacemaker leads, algorithmic and rate responsive programming―all have revolutionized and transformed the implantation and management of transvenous cardiac pacemaker (TV-PPM).

The efficacy of implantable cardioverter-defibrillators (ICD) for primary prevention of sudden cardiac death (SCD) has not been studied in patients with end-stage renal disease (ESRD) and left ventricular dysfunction. We sought to identify predictors of long-term survival among ICD recipients with and without ESRD. Methods Patients implanted with an ICD at our institution from January 2006 to March 2014 were retrospectively identified. Clinical and demographic characteristics were collected. Patients were stratified by the presence of ESRD at the time of ICD implant. Mortality data were collected from the Social Security Death Index (SSDI). Results A total of 3453 patients received an ICD at our institution in the pre-specified time period, 184 (5.3%) of whom had ESRD. In general, ESRD patients were sicker and had more comorbidities. Kaplan Meier survival curve showed that ESRD patients had worse survival as compared with non-dialysis patients (p < 0.001). Following adjustment for differences in baseline characteristics, patients with ESRD remained at increased long-term mortality in the Cox model. The one-year mortality in the ESRD patients was 18.1%, as compared with 7.7% in the non-dialysis cohort (p < 0.001). The three-year mortality in ESRD patients was 43%, as compared with 21% in the non-dialysis cohort (p < 0.001). Conclusion ESRD patients are at significantly increased risk of mortality as compared with a non-dialysis cohort. While the majority of these patients survive more than one year post-diagnosis, the three-year mortality is high (43%). Randomized studies addressing the benefits of ICDs in ESRD patients are needed to better define their value for primary prevention of SCD.

Background: Clinical outcomes of cardiac resynchronization therapy (CRT) in patients over the age of 80 have not been well described. Methods: We retrospectively identified 96 consecutive patients ≥ 80 years old who underwent an initial implant or an upgrade to CRT, with or without defibrillator (CRT-D vs. CRT-P), at our institution between January 2003 and July 2008. The control cohort consisted of 177 randomly selected patients < 80 years old undergoing CRT implant during the same time period. The primary efficacy endpoint was all-cause mortality at 36 months, assessed by Kaplan-Meier time to first event curves. Results: In the octogenarian cohort, mean age at CRT implant was 83.1 ± 2.9 years vs. 60.1 ± 8.8 years among controls (P < 0.001). Across both groups, 70% were male, mean left ventricular ejection fraction (LVEF) was 24.8% ± 14.1% and QRS duration was 154 ± 24.8 ms, without significant differences between groups. Octogenarians were more likely to have ischemic cardiomyopathy (74% vs. 37%, P < 0.001) and more likely to undergo upgrade to CRT instead of an initial implant (42% vs. 19%, P < 0.001). The rate of appropriate defibrillator shocks was lower among octogenarians (14% vs. 27%, P = 0.02) whereas the rate of inappropriate shocks was similar (3% vs. 6%, P = 0.55). At 36 months, there was no significant difference in the rate of all-cause mortality between octogenarians (11%) and controls (8%, P = 0.381). Conclusion: Appropriately selected octogenarians who are candidates for CRT have similar intermediate-term mortality compared to younger patients receiving CRT.

Introduction: Leadless pacemakers may provide a safe and attractive pacing option to patients with cardiac implantable electronic device (CIED) infection. We describe the characteristics and outcomes of patients with a recent CIED infection undergoing Micra implant attempt. Methods and Results: Patients with prior CIED infection and device explant with Micra implant within 30 days, were identified from the Micra post approval registry. Procedure characteristics and outcomes were summarized. A total of 105 patients with prior CIED infection underwent Micra implant attempt ≤30 days from prior system explant (84 [80%] pacemakers and 13 [12%] ICD/CRT-D). All system components were explanted in 93% of patients and explant occurred a median of 6 days before Micra implant, with 37% occurring on the day of Micra implant. Micra was successfully implanted in 99% patients, mean follow-up duration was 8.5 ± 7.1 months (range 0-28.5). The majority of patients (91%) received IV antibiotics preimplant, while 42% of patients received IV antibiotics postprocedure. The median length of hospitalization following Micra implant was 2 days (IQR, 1-7). During follow-up, two patients died from sepsis and four patients required system upgrade, of which two patients received Micra to provide temporary pacing support. There were no Micra devices explanted due to infection. Conclusion: Implantation of the Micra transcatheter pacemaker is safe and feasible in patients with a recent CIED infection. No recurrent infections that required Micra device removal were seen. Leadless pacemakers appear to be a safe pacing alternative for patients with CIED infection who undergo extraction.

Author reply: We would like to thank Dr. Madias for his interest in our article.1 This article suggests that QRS‐complex duration (QRSd) is associated with atrial fibrillation (AF) independent of several different indicators of heart‐failure severity, comorbid conditions, and medications known to reduce AF incidence. Hence came our conclusion: “In this large cohort of patients, QRSd was strongly associated with AF and therefore may predict the occurrence of this arrhythmia in patients with LV (left ventricular) dysfunction.” We agree with Dr. Madias that prediction of AF requires observational studies with long‐term follow‐up and monitoring for AF development and/or QRS widening. The major limitation of our manuscript is the retrospective nature of the study, which was acknowledged in the “Limitations” section of the article. We believe, however, that this study, like any other good retrospective study, produces more questions than answers. These questions will need to be addressed in a prospective manner. Hence, the conclusion that QRSd may predict the occurrence of AF in patients with LV dysfunction needs to be verified prospectively and longitudinally, as Dr. Madias suggested.