Rationale and Design of the Lead EvaluAtion for Defibrillation and Reliability (LEADR) Study: Safety and Efficacy of a Novel ICD Lead Design

Background: Implantable cardioverter defibrillators (ICD) are indicated for primary and secondary prevention of sudden cardiac arrest. Despite enhancements in design and technologies, the ICD lead is the most vulnerable component of the ICD system and failure of ICD leads remains a significant clinical problem. A novel, small diameter, lumenless, catheter delivered, defibrillator lead was developed with the aim to improve long term reliability. Methods and Results: The Lead Evaluation for Defibrillation and Reliability (LEADR) study is a multi-center, single-arm, Bayesian, adaptive design, pre-market interventional pivotal clinical study. Up to 60 study sites from around the world will participate in the study. Patients indicated for a de novo ICD will undergo defibrillation testing at implantation and clinical assessments at baseline, implant, pre-hospital discharge, 3 months, 6 months, and every 6 months thereafter until official study closure. Patients will participate for a minimum of 18 months to approximately 3 years. Fracture-free survival will be evaluated using a Bayesian statistical method that incorporates both virtual patient data (combination of bench testing to failure with in-vivo use condition data) with clinical patients. The clinical subject sample size will be determined using decision rules for number of subject enrollments and follow-up time based upon the observed number of fractures at certain time points in the study. The adaptive study design will therefore result in a minimum of 500 and a maximum of 900 patients enrolled. Conclusion: The LEADR Clinical Study was designed to efficiently provide evidence for short- and long-term safety and efficacy of a novel lead design using Bayesian methods including a novel virtual patient approach.

Ventricular Arrhythmias Among Patients With Advanced Heart Failure: A Population‐Based Study

Background The epidemiology of ventricular arrhythmias (VAs) in patients with advanced heart failure (HF) is not well defined. Methods and Results Residents of Olmsted County, Minnesota, with advanced HF from 2007 to 2017 were identified using the 2018 European Society of Cardiology criteria. Billing codes were used to capture VAs; severe VAs requiring emergency care were defined as events associated with emergency department visits or hospitalizations. The cumulative incidence of VAs postadvanced HF was estimated with the Kaplan–Meier method. Multivariable Cox analyses were used to determine the following: (1) Predictors of severe VAs postadvanced HF; and (2) Impact of severe VAs on mortality. Of 936 patients with advanced HF, 261 (27.9%) had a history of VA. The 1‐year cumulative incidence of severe VAs postadvanced HF was 5.4%. Prior VAs (hazard ratio [HR] 2.22 [95% CI, 1.26–3.89], P =0.006) and left ventricular ejection fraction <40% (HR, 3.79 [95% CI, 1.72–8.39], P <0.001) were independently associated with increased severe VA risk postadvanced HF. New‐onset severe VAs were associated with increased mortality (HR, 4.41 [95% CI, 2.80–6.94]; P <0.001), whereas severe VAs in patients with prior VAs had no significant association with mortality risk (HR, 1.08 [95% CI, 0.65–1.78]; P =0.77). Severe VAs were associated with increased mortality in patients without implantable cardioverter defibrillators (HR, 4.89 [95% CI, 2.89–8.26]; P <0.001), but not in patients with implantable cardioverter defibrillators (HR, 1.42 [95% CI, 0.92–2.19]; P =0.11). Conclusions Patients with left ventricular ejection fraction <40% and prior VAs have increased risk of severe VA postadvanced HF. New‐onset severe VAs or severe VAs without implantable cardioverter defibrillators postadvanced HF are associated with increased mortality.

CIED guideline recommendations in the setting of advisories

Subcutaneous implantable cardioverter defibrillators (S-ICDs) are currently indicated for patients who meet ICD implantation criteria for the prevention of sudden cardiac death (SCD). In December 2020, a unique cardiac implantable electronic device (CIED) situation arose as both the S-ICD generator and electrode were under a device advisory. We would recommend all future CIED implantation guidelines receive a caveat regarding checking current CIED advisories, in order to avoid future similar scenarios.

Efficacy and Complications of Subcutaneous versus Conventional Cardioverter Defibrillators: A Systematic Review and Meta-Analysis

Background/Objectives: Implantable cardioverter defibrillators are used to prevent sudden cardiac death. The subcutaneous implantable cardioverter defibrillator was newly developed to overcome the limitations of the conventional implantable cardioverter defibrillator-transvenous device. The subcutaneous implantable cardioverter defibrillator is indicated for young patients with heart disease, congenital heart defects, and poor venous access, who have an indication for implantable cardioverter defibrillator without the need for anti-bradycardic stimulation. We aimed to compare the efficacy and complications of subcutaneous with transvenous implantable cardioverter defibrillator devices. Methodology: A systematic review was conducted using different databases. The inclusion criteria were observational and clinical randomized trials with no language limits and no publication date limit that compared subcutaneous with transvenous implantable cardioverter defibrillators. The selected patients were aged > 18 years with complex ventricular arrhythmia. Results : Five studies involving 2111 patients who underwent implantable cardioverter defibrillator implantation were included. The most frequent complication in the subcutaneous device group was infection, followed by hematoma formation and electrode migration. For the transvenous device, the most frequent complications were electrode migration and infection. Regarding efficacy, the total rates of appropriate shocks were 9.04% and 20.47% in the subcutaneous and transvenous device groups, respectively, whereas inappropriate shocks to the subcutaneous and transvenous device groups were 11,3% and 10,7%, respectively. Conclusion: When compared to the transvenous device, the subcutaneous device had lower complication rates owing to lead migration and less inappropriate shocks due to supraventricular tachycardia; nevertheless, infection rates and improper shocks due to T wave oversensing were comparable for both devices

Microvolt QRS Alternans in Hypertrophic Cardiomyopathy: A Novel Risk Marker of Late Ventricular Arrhythmias

Background Unlike T‐wave alternans (TWA), the relation between QRS alternans (QRSA) and ventricular arrhythmia (VA) risk has not been evaluated in hypertrophic cardiomyopathy (HCM). We assessed microvolt QRSA/TWA in relation to HCM risk factors and late VA outcomes in HCM. Methods and Results Prospectively enrolled patients with HCM (n=130) with prophylactic implantable cardioverter‐defibrillators underwent digital 12‐lead ECG recordings during ventricular pacing (100–120 beats/min). QRSA/TWA was quantified using the spectral method. Patients were categorized as QRSA+ and/or TWA+ if sustained alternans was present in ≥2 precordial leads. The VA end point was appropriate implantable cardioverter‐defibrillator therapy over 5 years of follow‐up. QRSA+ and TWA+ occurred together in 28% of patients and alone in 7% and 7% of patients, respectively. QRSA magnitude increased with pacing rate (1.9±0.6 versus 6.2±2.0 µV; P =0.006). Left ventricular thickness was greater in QRSA+ than in QRSA− patients (22±7 versus 20±6 mm; P =0.035). Over 5 years follow‐up, 17% of patients had VA. The annual VA rate was greater in QRSA+ versus QRSA− patients (5.8% versus 2.0%; P =0.006), with the QRSA+/TWA− subgroup having the greatest rate (13.3% versus 2.6%; P <0.001). In those with <2 risk factors, QRSA− patients had a low annual VA rate compared QRSA+ patients (0.58% versus 7.1%; P =0.001). Separate Cox models revealed QRSA+ (hazard ratio [HR], 2.9 [95% CI, 1.2–7.0]; P =0.019) and QRSA+/TWA− (HR, 7.9 [95% CI, 2.9–21.7]; P <0.001) as the most significant VA predictors. TWA and HCM risk factors did not predict VA. Conclusions In HCM, microvolt QRSA is a novel, rate‐dependent phenomenon that can exist without TWA and is associated with greater left ventricular thickness. QRSA increases VA risk 3‐fold in all patients, whereas the absence of QRSA confers low VA risk in patients with <2 risk factors. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02560844.

Advances in Cardiac Pacing: Arrhythmia Prediction, Prevention and Control Strategies

Cardiac arrhythmias constitute a tremendous burden on healthcare and are the leading cause of mortality worldwide. An alarming number of people have been reported to manifest sudden cardiac death as the first symptom of cardiac arrhythmias, accounting for about 20% of all deaths annually. Furthermore, patients prone to atrial tachyarrhythmias such as atrial flutter and fibrillation often have associated comorbidities including hypertension, ischemic heart disease, valvular cardiomyopathy and increased risk of stroke. Technological advances in electrical stimulation and sensing modalities have led to the proliferation of medical devices including pacemakers and implantable defibrillators, aiming to restore normal cardiac rhythm. However, given the complex spatiotemporal dynamics and non-linearity of the human heart, predicting the onset of arrhythmias and preventing the transition from steady state to unstable rhythms has been an extremely challenging task. Defibrillatory shocks still remain the primary clinical intervention for lethal ventricular arrhythmias, yet patients with implantable cardioverter defibrillators often suffer from inappropriate shocks due to false positives and reduced quality of life. Here, we aim to present a comprehensive review of the current advances in cardiac arrhythmia prediction, prevention and control strategies. We provide an overview of traditional clinical arrhythmia management methods and describe promising potential pacing techniques for predicting the onset of abnormal rhythms and effectively suppressing cardiac arrhythmias. We also offer a clinical perspective on bridging the gap between basic and clinical science that would aid in the assimilation of promising anti-arrhythmic pacing strategies.

303 Longitudinal arrhythmic risk assessment based on ejection fraction in patients with recent-onset non-ischaemic dilated cardiomyopathy

Aims Practice guidelines suggest implantable cardioverter defibrillators (ICD) in patients with left ventricular ejection fraction (LVEF) ≤35% despite 3–6 months of guideline-directed medical therapy (GDMT). It remains unclear whether this strategy is appropriate for patients with dilated cardiomyopathy (DCM), who can experience reverse ventricular remodelling for up to 24 months after initiation of GDMT. We sought to assess the longitudinal dynamic relationship between LVEF ≤35% and arrhythmic risk in patients with recent onset non-ischaemic DCM under GDMT. Methods and results We performed a competitive risk analysis on patients with recent onset DCM (≤6 months) and recent initiation of GDMT (≤3 months), consecutively enrolled in a longitudinal registry. We assessed risk of major ventricular arrhythmic events or sudden cardiac death (MVAs/SCD) in relationship to LVEF ≤35% at enrollment, 6-months and 24-months post initiation of GDMT. 544 patients met inclusion criteria. LVEF ≤35% identified patients with increased risk of MVAs/SCD starting from 24-months after initiation of GDMT (hazards ratio: 2.126, 95% confidence interval: 1.065–4.245, P = 0.03). However, LVEF ≤35% at presentation or at 6 months post enrollment did not have prognostic significance. 67% of patients with LVEF ≤35% at 6 months after initiation of GDMT improved their LVEF to &gt; 35% by 24 months. This late LVEF improvement correlated with a lower arrhythmic risk (P = 0.012) and was preceded by a reduction of LV dimensions in the first 6 months of GDMT. Conclusions In patients with DCM, risk stratification based on LVEF ≤35% is effective after 2 years of GDMT, but not after 6 months.

Perceived Control and ICD Concerns in Older ICD Recipients: Sex as a Moderator

Implantable cardioverter defibrillators (ICDs) reduce the risk of sudden cardiac death for those with a history of or high risk for lethal arrhythmias. In 2016, 105,000 ICDs were implanted in older adults (age ≥ 60) in the US. Approximately 25% of ICD recipients report significant ICD concerns with women reporting higher levels than men. Little is known about the experience of older adults living with life-saving/extending medical technologies, particularly related to sex differences in ICD concerns. Perceived control may decrease ICD concerns, but sex differences have not been explored. The aim of this cross-sectional study was to determine the moderation effect of sex on the association between perceived control and ICD concerns in older adults (age≥ 60). Participants completed a questionnaire on ICD Concerns (ICDC-8) and the Control Attitudes Scale-Revised, a measure of perceived control. We conducted a moderation analysis using Hayes’ PROCESS for SPSS with 5,000 bootstrap samples. Of the 99 participants (73.7% male; age 70 + 7 years; education 13 + 3 years), most participants were white (79.8%) and married (69.7%). There were no differences in participant characteristics, perceived control, or ICD concerns, by sex. We found an interaction between sex and perceived control (b= -.5715, p= 02), indicating that for women (-.5801, p =.007), as perceived control increased, ICD concerns decreased. For men (-.0089, p =.9439), ICD concerns remained the same despite level of perceived control. Future clinical and research interventions to decrease ICD concerns should include ways to increase perceived control particularly for older women living with ICDs.