© 2015 Hartlage et al. Background: Despite marked benefits in many heart failure patients, a considerable proportion of patients treated with cardiac resynchronization therapy (CRT) fail to respond appropriately. Recently, a "U-shaped" (type II) wall motion pattern identified by cardiovascular magnetic resonance (CMR) has been associated with improved CRT response compared to a homogenous (type I) wall motion pattern. There is also evidence that a left ventricular (LV) lead localized to the latest contracting LV site predicts superior response, compared to an LV lead localized remotely from the latest contracting LV site. Methods: We prospectively evaluated patients undergoing CRT with pre-procedural CMR to determine the presence of type I and type II wall motion patterns and pre-procedural echocardiography to determine end systolic volume (ESV). We assessed the final LV lead position on post-procedural fluoroscopic images to determine whether the lead was positioned concordant to or remote from the latest contracting LV site. CRT response was defined as ≥15 % reduction in ESV on a 6 month follow-up echocardiogram. Results: The study included 33 patients meeting conventional indications for CRT with a mean New York Heart Association class of 2.8 ± 0.4 and mean LV ejection fraction of 28 ± 9 %. Overall, 55 % of patients were echocardiographic responders by ESV criteria. Patients with both a type II pattern and an LV lead concordant to the latest contracting site (T2CL) had a response rate of 92 %, compared to a response rate of 33 % for those without T2CL (p = 0.003). T2CL was the only independent predictor of response on multivariate analysis (odds ratio 18, 95 % confidence interval 1.6-206; p = 0.018). T2CL resulted in significant incremental improvement in prediction of echocardiographic response (increase in the area under the receiver operator curve from 0.69 to 0.84; p = 0.038). Conclusions: The presence of a type II wall motion pattern on CMR and a concordant LV lead predicts superior CRT response. Improving patient selection by evaluating wall motion pattern and targeting LV lead placement may ultimately improve the response rate to CRT.

Aims: The subcutaneous implantable cardioverter defibrillator (S-ICD) was introduced to overcome complications related to transvenous leads. Adoption of the S-ICD requires implanters to learn a new implantation technique. The aim of this study was to assess the learning curve for S-ICD implanters with respect to implant-related complications, procedure time, and inappropriate shocks (IASs). Methods and results: In a pooled cohort from two clinical S-ICD databases, the IDE Trial and the EFFORTLESS Registry, complications, IASs at 180 days follow-up and implant procedure duration were assessed. Patients were grouped in quartiles based on experience of the implanter and Kaplan-Meier estimates of complication and IAS rates were calculated. A total of 882 patients implanted in 61 centres by 107 implanters with a median of 4 implants (IQR 1,8) were analysed. There were a total of 59 patients with complications and 48 patients with IAS. The complication rate decreased significantly from 9.8% in Quartile 1 (least experience) to 5.4% in Quartile 4 (most experience) (P = 0.02) and non-significantly for IAS from 7.9 to 4.8% (P = 0.10). Multivariable analysis demonstrated a hazard ratio of 0.78 (P = 0.045) for complications and 1.01 (P = 0.958) for IAS. Dual-zone programming increased with experience of the individual implanter (P < 0.001), which reduced IAS significantly in the multivariable model (HR 0.44, P = 0.01). Procedure time decreased from 75 to 65 min (P < 0.001). The complication rate and procedure time stabilized after Quartile 2 ( > 13 implants). Conclusion: There is a short and significant learning curve associated with physicians adopting the S-ICD. Performance stabilizes after 13 implants.

Background: Head-to-head comparative data for the postoperative care of patients undergoing left atrial ablation procedures are lacking. Objective: We sought to investigate complication and readmission rates between patients undergoing same-day (SD) or next-day (ND) discharges for ablative procedures in the left atrium, primarily atrial fibrillation (AF). Methods: Two electrophysiology centers simultaneously perform left atrial ablations with differing discharge strategies. We identified all patients who underwent left atrial ablation from August 2017 to August 2019 (n = 409) undergoing either SD (n = 210) or ND (n = 199) discharge protocols. We analyzed any clinical events that resulted in procedural abortion, extended hospitalization, or readmission within 72 hours. Results: The primary endpoint of complication and readmission rate was similar between SD and ND discharge (14.3% vs 12.6%, p = 0.665). Rates of complications categorized as major (2.4% vs 3.0%, p = 0. 776) and minor (11.9% vs 9.5%, p = 0.524) were also similar. Multivariable regression modeling revealed no significant correlation between discharge strategy and complication/readmission occurrence (OR 1.565 [0.754 – 3.248], p = 0.23), but a positive association of hypertension and procedure duration (OR 3.428 [1.436 – 8.184], p = 0.006) and (OR 1.01 [1 – 1.019], p = 0.046) respectively. Conclusions: Left atrial ablation complication and readmission rates were similar between SD and ND discharge practices. Hypertension and procedural duration were associated with increased complication rates irrespective of discharge strategy. These data, which represent the first side-by-side comparison of discharge strategy, suggests same-day discharge is safe and feasible for left atrial ablation procedures.

Background: Cancer treatment induced arrhythmia (CTIA) is a well-recognized form of cardiotoxicity associated with chemotherapy. Immune checkpoint inhibitors (ICI) have been associated with important forms of cardiotoxicity, including myocarditis. However, the incidence of CTIA associated with ICI has not been well characterized. Methods: We reviewed all patients treated with ICIs at our institution from Jan. 2010 to Oct. 2015. CTIA was defined as a new diagnosis of clinically relevant arrhythmia within 6 months after ICI initiation. Results: During the study period, 268 patients were treated with immune checkpoint inhibitors, of whom 190 received monotherapy with ipilimumab (n=114), nivolumab (n=52) or pembrolizumab (n=24) and 78 received combination therapy: ipilimumab & nivolumab (n=37), ipilimumab & pembrolizumab (n=39) and nivolumab & pembrolizumab (n=2). Four patients (1.5%) developed CTIA. Of these, 3 patients developed a new diagnosis of atrial fibrillation (AF), one of whom required cardioversion. In 2 cases of new-onset AF, significant provoking factors were present in addition to ICI therapy including thyrotoxicosis in one and metabolic disarray in another. Six patients (2.2%) with a pre-existing diagnosis of paroxysmal AF experienced episodes within 6 months of initiating ICI therapy. None of the arrhythmic events were associated with known or suspected myocarditis. Conclusion: The incidence of arrhythmic complications associated with immune checkpoint inhibitors appears to be very low (~1.5%). Patients with a pre-existing diagnosis of AF may be at-risk of recurrence during ICI treatment and should be monitored accordingly. These data suggest that from an arrhythmia perspective, ICIs appear to be very safe and well-tolerated.

Background: Left ventricular dyssynchrony is often diagnosed by comparing velocity curves from Doppler tissue images of two or more myocardial regions. Velocity curves are generated by placing sample volumes or regions of interest (ROIs) within the myocardium. ROIs need to be manually relocated to maintain a midmyocardial location as the heart moves, but are frequently left in a stationary position. The error caused by use of a stationary ROI may affect the diagnosis of dyssynchrony, but this has not been quantified. Objective: We hypothesized that using a stationary ROI to quantify dyssynchrony from Doppler tissue images would affect the diagnosis of dyssynchrony in patients with heart failure. Methods: We quantified dyssynchrony in 18 patients with heart failure using 4 published dyssynchrony parameters: septal-to-lateral delay, maximum difference in the basal 2- or 4-chamber times to peak, SD of the 12 basal and midwall times to peak, and cross-correlation delay (XCD). Each dyssynchrony parameter was measured using both tracked and stationary ROIs. Results: Use of a stationary ROI did not change the diagnosis of dyssynchrony when using XCD. However, ROI tracking changed the diagnosis of dyssynchrony in 17%, 11%, and 17% of patients when using septal-to-lateral delay, maximum difference in the basal 2- or 4-chamber times to peak, and SD of the 12 basal and midwall times to peak, respectively. XCD showed the lowest percent difference between tracked and stationary ROIs (4 ± 9% vs 22 ± 53%, 50 ± 167%, and 12 ± 30%, respectively, for septal-to-lateral delay, maximum difference in the basal 2- or 4-chamber times to peak, and SD of the 12 basal and midwall times to peak). Conclusion: Manual ROI tracking is required when using conventional time-to-peak parameters to diagnose dyssynchrony. XCD diagnosis of dyssynchrony can be performed accurately with a stationary ROI.

Background: QRSduration (QRSd) is associated with higher mortality and morbidity in patients with left ventricular (LV) dysfunction. The association between QRSd and atrial fibrillation (AF) has not been studied in this patient population. Objectives: To investigate the association between QRSd and AF in patients with LV dysfunction. Methods: Data were obtained from the National Registry to Advance Heart Health (ADVANCENT) registry, a prospective multicenter registry of patients with left ventricular ejection fraction (LVEF) ≤40%. A total of 25 268 patients from106 centers in the United States, were enrolled between June 2003 and November 2004. Demographic and clinical characteristics of patientswere collected from interviews and medical records. Results: Mean age was 66.3 ± 13 years, 71.5% were males, and 81.9% were white. A total of 14 452 (57.8%) patients had a QRSd <120 ms, 5304 (21.2%) had a QRSd between 120 and 150 ms, and 5269 (21%) had a QRSd >150 ms. Atrial fibrillation occurred in 20.9%, 27.5%, and 35.5% of patients in the QRS groups, respectively (P < 0.0001). After adjusting for potential AF risk factors (age, gender, race, body mass index, hypertension, diabetes, renal failure, cancer, lung disease, New York Heart Association [NYHA] class, ejection fraction, etiology of cardiomyopathy) and the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and lipid lowering drugs, QRS duration remained independently associated with AF (odds ratio: 1.20, 95% confidence interval: 1.14-1.25). Conclusion: In this large cohort of patients, QRSd was strongly associated with AF and thereforemay predict the occurrence of this arrhythmia in patients with LV dysfunction. This association persisted after adjusting for disease severity, comorbid conditions, and the use of medications known to be protective against AF.

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.

Purpose: To apply cross-correlation delay (XCD) analysis to myocardial phase contrast magnetic resonance (PCMR) tissue velocity data and to compare XCD to three established "time-to-peak" dyssynchrony parameters. Materials and Methods: Myocardial tissue velocity was acquired using PCMR in 10 healthy volunteers (negative controls) and 10 heart failure patients who met criteria for cardiac resynchronization therapy (positive controls). All dyssynchrony parameters were computed from PCMR velocity curves. Sensitivity, specificity, and receiver operator curve (ROC) analysis for separating positive and negative controls were computed for each dyssynchrony parameter. Results: XCD had higher sensitivity (90%) and specificity (100%) for discriminating between normal and patient groups than any of the time-to-peak dyssynchrony parameters. ROC analysis showed that XCD was the best parameter for separating the positive and negative control groups. Conclusion:XCD is superior to time-to-peak dyssynchrony parameters for discriminating between subjects with and without dyssynchrony and may aid in the selection of patients for cardiac resynchronization therapy.