Patient-reported quality of life and acceptance of the extravascular implantable cardioverter-defibrillator: Results from pivotal study.

INTRODUCTION: The pivotal study of the extravascular implantable cardioverter-defibrillator (EV ICD) recently demonstrated primary efficacy and safety endpoints comparable to previous ICD systems. Patient experience with this novel device has not been reported. The current study examined the standardized patient-reported outcome (PRO) metrics of quality of life (QOL) and patient acceptance of the device. METHODS: The EV ICD Pivotal Study was a prospective, single-arm, nonrandomized, global, premarket approval trial. Patients completed the 12-Item Short Form Survey (SF-12) QOL surveys at baseline and at 6 months following implant. Additionally, patients completed the Florida Patient Acceptance Survey (FPAS) QOL survey at 6 months. RESULTS: From baseline to 6 months, patients within the EV ICD Pivotal Study (n = 247) reported statistically significant SF-12 improvements in physical QOL (45.4 ± 9.4 vs. 46.8 ± 9.1 respectively, p = .020) and no changes in mental QOL (49.3 ± 10.4 vs. 50.5 ± 9.7, p = .061). No differences were noted by sex, atrial fibrillation, or the experience of ICD shock. EV ICD patients reported better total FPAS patient acceptance of their ICD than TV-ICD or S-ICD patients using historical norms comparisons (80.4 ± 15.7 vs. 70.2 ± 17.8, p < .0001 for S-ICD and 73.0 ± 17.4, p = .004 for TV-ICD). CONCLUSION: The initial PROs for EV ICD patients indicated that patients had improvements in physical QOL from baseline to 6-month follow-up and markedly better overall acceptance of their ICD compared to a previous study with S-ICD and TV-ICD data. These initial results suggest that the EV ICD is evaluated positively by patients.

An International Survey of Current Clinical Practice in the Treatment of Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is a potentially serious form of infiltrative cardiomyopathy. Despite scarce evidence, immunosuppressive treatment is generally recommended, but local routines may vary significantly. We sought to survey the clinical practices in the treatment of CS, with the aim that the results may suggest future research priorities. We conducted a web-based survey focused on treatment-naive patients with CS. We subclassified CS according to the presence/absence of overt cardiac presentation (clinically manifest/silent) and to the presence/absence of active inflammation (metabolically active/inactive by fluorodeoxyglucose positron emission tomography). The survey was developed jointly by the authors and administered to expert clinicians (n = 79) involved in CS treatment. An agreement threshold was set at 70%. A total of 62 of 79 respondents (78.5%) from 12 countries completed the survey. The agreement threshold was reached for: (1) always treating clinically manifest, metabolically active CS, 57 of 62 (91.9%), (2) never treating clinically silent, metabolically inactive CS, 44 of 62 (71.0%), (3) not requiring histopathologic confirmation of sarcoidosis before treatment initiation, (49 of 62, 79.0%), (4) using fluorodeoxyglucose positron emission tomography for assessing treatment indication (44 of 62, 71.0%) and treatment response (44 of 62, 71.0%), and (5) using prednisone as a first-line agent (100%), although respondents were divided on monotherapy (69.4%) or combination with methotrexate 25.8%. The approach to particular scenarios, tapering, and duration of treatment showed the greatest variation in response. In conclusion, in this survey of clinical practice, important aspects of CS treatment reached the agreement threshold, whereas others showed a great degree of clinical equipoise.

Risk of Adverse Outcomes Associated With Cardiac Sarcoidosis Diagnostic Schemes.

BACKGROUND: Multiple cardiac sarcoidosis (CS) diagnostic schemes have been published. OBJECTIVES: This study aims to evaluate the association of different CS diagnostic schemes with adverse outcomes. The diagnostic schemes evaluated were 1993, 2006, and 2017 Japanese criteria and the 2014 Heart Rhythm Society criteria. METHODS: Data were collected from the Cardiac Sarcoidosis Consortium, an international registry of CS patients. Outcome events were any of the following: all-cause mortality, left ventricular assist device placement, heart transplantation, and appropriate implantable cardioverter-defibrillator therapy. Logistic regression analysis evaluated the association of outcomes with each CS diagnostic scheme. RESULTS: A total of 587 subjects met the following criteria: 1993 Japanese (n = 310, 52.8%), 2006 Japanese (n = 312, 53.2%), 2014 Heart Rhythm Society (n = 480, 81.8%), and 2017 Japanese (n = 112, 19.1%). Patients who met the 1993 criteria were more likely to experience an event than patients who did not (n = 109 of 310, 35.2% vs n = 59 of 277, 21.3%; OR: 2.00; 95% CI: 1.38-2.90; P < 0.001). Similarly, patients who met the 2006 criteria were more likely to have an event than patients who did not (n = 116 of 312, 37.2% vs n = 52 of 275, 18.9%; OR: 2.54; 95% CI: 1.74-3.71; P < 0.001). There was no statistically significant association between the occurrence of an event and whether a patient met the 2014 or the 2017 criteria (OR: 1.39; 95% CI: 0.85-2.27; P = 0.18 or OR: 1.51; 95% CI: 0.97-2.33; P = 0.067, respectively). CONCLUSIONS: CS patients who met the 1993 and the 2006 criteria had higher odds of adverse clinical outcomes. Future research is needed to prospectively evaluate existing diagnostic schemes and develop new risk models for this complex disease.

Syncope in ICD recipients: a single centre experience.

AIMS: There is little evidence of the impact of syncope in implantable cardioverter-defibrillator (ICD) patients in routine community hospital care. This single-centre retrospective study sought to evaluate the incidence and prognostic significance of syncope in consecutive ICD patients. METHODS AND RESULTS: Data were collected on consecutive patients undergoing first ICD implantation between January 2009 and December 2019. The primary endpoints were the first occurrence of all-cause syncope, all-cause mortality, and all-cause hospitalization. Multivariate Cox proportional hazard models were used to identify risk factors associated with syncope and to analyse the subsequent risk of mortality and hospitalization. 1003 patients (58% primary prevention) were included in the final analysis. During a mean follow-up of 1519 ± 1055 days, 106 (10.6%) experienced syncope, 304 died (30.3%), and 477 (47.5%) were hospitalized for any cause. In an analysis adjusted for baseline variables, the first occurrence of syncope was associated with a significantly increased risk of mortality (HR 2.82, P < 0.001) and the first occurrence of hospitalization (HR 2.46, P = 0.002). CONCLUSION: Syncope in ICD recipients is common and associated with a poor prognosis irrespective of baseline variables and ICD programming. The occurrence of syncope is associated with a significant increase in the risk of mortality and hospitalization.

Efficacy and Safety of an Extravascular Implantable Cardioverter-Defibrillator.

BACKGROUND: The extravascular implantable cardioverter-defibrillator (ICD) has a single lead implanted substernally to enable pause-prevention pacing, antitachycardia pacing, and defibrillation energy similar to that of transvenous ICDs. The safety and efficacy of extravascular ICDs are not yet known. METHODS: We conducted a prospective, single-group, nonrandomized, premarket global clinical study involving patients with a class I or IIa indication for an ICD, all of whom received an extravascular ICD system. The primary efficacy end point was successful defibrillation at implantation. The efficacy objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients with successful defibrillation was greater than 88%. The primary safety end point was freedom from major system- or procedure-related complications at 6 months. The safety objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients free from such complications was greater than 79%. RESULTS: A total of 356 patients were enrolled, 316 of whom had an implantation attempt. Among the 302 patients in whom ventricular arrhythmia could be induced and who completed the defibrillation testing protocol, the percentage of patients with successful defibrillation was 98.7% (lower boundary of the one-sided 97.5% confidence interval [CI], 96.6%; P<0.001 for the comparison with the performance goal of 88%); 299 of 316 patients (94.6%) were discharged with a working ICD system. The Kaplan-Meier estimate of the percentage of patients free from major system- or procedure-related complications at 6 months was 92.6% (lower boundary of the one-sided 97.5% CI, 89.0%; P<0.001 for the comparison with the performance goal of 79%). No major intraprocedural complications were reported. At 6 months, 25 major complications were observed, in 23 of 316 patients (7.3%). The success rate of antitachycardia pacing, as assessed with generalized estimating equations, was 50.8% (95% CI, 23.3 to 77.8). A total of 29 patients received 118 inappropriate shocks for 81 arrhythmic episodes. Eight systems were explanted without extravascular ICD replacement over the 10.6-month mean follow-up period. CONCLUSIONS: In this prospective global study, we found that extravascular ICDs were implanted safely and were able to detect and terminate induced ventricular arrhythmias at the time of implantation. (Funded by Medtronic; ClinicalTrials.gov number, NCT04060680.).

Power Modulation Echocardiography to Detect and Quantify Myocardial Scar.

BACKGROUND: Myocardial scar correlates with clinical outcomes. Traditionally, late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is used to detect and quantify scar. In this prospective study using LGE CMR as reference, the authors hypothesized that nonlinear ultrasound imaging, namely, power modulation, can detect and quantify myocardial scar in selected patients with previous myocardial infarction. In addition, given the different histopathology between ischemic and nonischemic scar, a further aim was to test the diagnostic performance of this echocardiographic technique in unselected consecutive individuals with ischemic and nonischemic LGE or no LGE on CMR. METHODS: Seventy-one patients with previous myocardial infarction underwent power modulation echocardiography following CMR imaging (group A). Subsequently, 101 consecutive patients with or without LGE on CMR, including individuals with nonischemic LGE, were scanned using power modulation echocardiography (group B). RESULTS: In group A, echocardiography detected myocardial scar in all 71 patients, with good scar volume agreement with CMR (bias = -1.9 cm3; limits of agreement [LOA], -8.0 to 4.2 cm3). On a per-segment basis, sensitivity was 82%, specificity 97%, and accuracy 92%. Sensitivity was higher in the inferior and posterior segments and lower in the anterior and lateral walls. In group B, on a per-subject basis, the sensitivity of echocardiography was 62% (91% for ischemic and 30% for nonischemic LGE), with specificity and accuracy of 89% and 72%, respectively. The bias for scar volume between modalities was 5.9 cm3, with LOA of 34.6 to 22.9 cm3 (bias = -1.9 cm3 [LOA, -11.4 to 7.6 cm3] for ischemic LGE, and bias = 18.9 cm3 [LOA, -67.4 to 29.7.6 cm3] for nonischemic LGE). CONCLUSIONS: Power modulation echocardiography can detect myocardial scar in both selected and unselected individuals with previous myocardial infarction and has good agreement for scar volume quantification with CMR. In an unselected cohort with nonischemic LGE, sensitivity is low.

The development of the extravascular defibrillator with substernal lead placement: A new Frontier for device-based treatment of sudden cardiac arrest.

INTRODUCTION: The extravascular implantable cardioverter-defibrillato (EV ICD) system with substernal lead placement is a novel nontransvenous alternative to current commercially available ICD systems. The EV ICD provides defibrillation and pacing therapies without the potential long-term complications of endovascular lead placement but requires a new procedure for implantation with a safety profile under evaluation. METHODS: This paper summarizes the development of the EV ICD, including the preclinical and clinical evaluations that have contributed to the system and procedural refinements to date. RESULTS: Extensive preclinical research evaluations and four human clinical studies with >140 combined acute and chronic implants have enabled the development and refinement of the EV ICD system, currently in worldwide pivotal study. CONCLUSION: The EV ICD may represent a clinically valuable solution in protecting patients from sudden cardiac death while avoiding the long-term consequences of transvenous hardware. The EV ICD offers advantages over transvenous and subcutaneous systems by avoiding placement in the heart and vasculature; relative to subcutaneous systems, EV ICD requires less energy for defibrillation, enabling a smaller device, and provides pacing features such as antitachycardia and asystole pacing in a single system.

Standard care vs. TRIVEntricular pacing in Heart Failure (STRIVE HF): a prospective multicentre randomized controlled trial of triventricular pacing vs. conventional biventricular pacing in patients with heart failure and intermediate QRS left bundle branch block.

AIMS: To determine whether triventricular (TriV) pacing is feasible and improves CRT response compared to conventional biventricular (BiV) pacing in patients with left bundle branch block (LBBB) and intermediate QRS prolongation (120-150 ms). METHODS AND RESULTS: Between October 2015 and November 2019, 99 patients were recruited from 11 UK centres. Ninety-five patients were randomized 1:1 to receive TriV or BiV pacing systems. The primary endpoint was feasibility of TriV pacing. Secondary endpoints assessed symptomatic and remodelling response to CRT. Baseline characteristics were balanced between groups. In the TriV group, 43/46 (93.5%) patients underwent successful implantation vs. 47/49 (95.9%) in the BiV group. Feasibility of maintaining CRT at 6 months was similar in the TriV vs. BiV group (90.0% vs. 97.7%, P = 0.191). All-cause mortality was similar between TriV vs. BiV groups (4.3% vs. 8.2%, P = 0.678). There were no significant differences in echocardiographic LV volumes or clinical composite scores from baseline to 6-month follow-up between groups. CONCLUSION: Implantation of two LV leads to deliver and maintain TriV pacing at 6 months is feasible without significant complications in the majority of patients. There was no evidence that TriV pacing improves CRT response or provides additional clinical benefit to patients with LBBB and intermediate QRS prolongation and cannot be recommended in this patient group. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT02529410.

Subcutaneous implantable cardioverter-defibrillators: long-term results of the EFFORTLESS study.

AIMS: To report 5-year outcomes of EFFORTLESS registry patients with early generation subcutaneous implantable cardioverter-defibrillator (S-ICD) devices. METHODS AND RESULTS: Kaplan-Meier, trend and multivariable analyses were performed for mortality and late (years 2-5) complications, appropriate shock (AS) and inappropriate shock (IAS) rates. Nine hundred and eighty-four of 994 enrolled patients with diverse diagnoses (28% female, 48 ± 17 years, body mass index 27 ± 6 kg/m2, ejection fraction 43 ± 18%) underwent S-ICD implantation. Median follow-up was 5.1 years (interquartile range 4.7-5.5 years). All-cause mortality was 9.3% (95% confidence interval 7.2-11.3%) at 5 years; 703 patients remained in follow-up on study completion, 171 withdrew including 87 (8.8%) with device explanted, and 65 (6.6%) lost to follow-up. Of the explants, only 20 (2.0%) patients needed a transvenous device for pacing indications. First and final shock efficacy for discrete ventricular arrhythmias was consistent at 90% and 98%, respectively, with storm episode final shock efficacy at 95.2%. Time to therapy remained unaltered. Overall 1- and 5-year complication rates were 8.9% and 15.2%, respectively. Early complications did not predict later complications. There were no structural lead failures. Inappropriate shock rates at 1 and 5 years were 8.7% and 16.9%, respectively. Self-terminating inappropriately sensed episodes predicted late IAS. Predictors of late AS included self-terminating appropriately sensed episodes and earlier AS. CONCLUSION: In this diverse S-ICD registry population, spontaneous shock efficacy was consistently high over 5 years. Very few patients underwent S-ICD replacement with a transvenous device for pacing indications. Treated and self-terminating arrhythmic episodes predict future shock events, which should encourage more personalized device optimization.

Outcomes Associated With Catheter Ablation of Ventricular Tachycardia in Patients With Cardiac Sarcoidosis.

Importance: Ventricular tachycardia (VT) is associated with high mortality in patients with cardiac sarcoidosis (CS), and medical management of CS-associated VT is limited by high failure rates. The role of catheter ablation has been investigated in small, single-center studies. Objective: To investigate outcomes associated with VT ablation in patients with CS. Design, Setting, and Participants: This cohort study from the Cardiac Sarcoidosis Consortium registry (2003-2019) included 16 tertiary referral centers in the US, Europe, and Asia. A total of 158 consecutive patients with CS and VT were included (33% female; mean [SD] age, 52 [11] years; 53% with ejection fraction [EF] <50%). Exposures: Catheter ablation of CS-associated VT and, as appropriate, medical treatment. Main Outcomes and Measures: Immediate and short-term outcomes included procedural success, elimination of VT storm, and reduction in defibrillator shocks. The primary long-term outcome was the composite of VT recurrence, heart transplant (HT), or death. Results: Complete procedural success (no inducible VT postablation) was achieved in 85 patients (54%). Sixty-five patients (41%) had preablation VT storm that did not recur postablation in 53 (82%). Defibrillator shocks were significantly reduced from a median (IQR) of 2 (1-5) to 0 (0-0) in the 30 days before and after ablation (P < .001). During median (IQR) follow-up of 2.5 (1.1-4.9) years, 73 patients (46%) experienced VT recurrence and 81 (51%) experienced the composite primary outcome. One- and 2-year rates of survival free of VT recurrence, HT, or death were 60% and 52%, respectively. EF less than 50% and myocardial inflammation on preprocedural 18F-fluorodeoxyglucose positron emission tomography were significantly associated with adverse prognosis in multivariable analysis for the primary outcome (HR, 2.24; 95% CI, 1.37-3.64; P = .001 and HR, 2.93; 95% CI, 1.31-6.55; P = .009, respectively). History of hypertension was associated with a favorable long-term outcome (adjusted HR, 0.51; 95% CI, 0.28-0.92; P = .02). Conclusions and Relevance: In this observational study of selected patients with CS and VT, catheter ablation was associated with reductions in defibrillator shocks and recurrent VT storm. Preablation LV dysfunction and myocardial inflammation were associated with adverse long-term prognosis. These data support the role of catheter ablation in conjunction with medical therapy in the management of CS-associated VT.

Generic ICD programming and outcomes.

INTRODUCTION: Generic ICD programming, where shock-reduction programming is extrapolated from trials of one manufacturer to another, may reduce non-essential ICD therapies beyond that seen in randomized trials. However, the benefits and risks are unknown. The purpose of this retrospective cohort study was to evaluate the impact of a standardized programming protocol, based on generic programming, across manufacturers. METHODS: We included all new ICDs in a single center (2009-2019). In 2013 a standardized programming protocol based on generic programming was introduced, incorporating high detection rates (200 bpm for primary prevention) and long detection (30/40 or equivalent in VF zone) for all patients. Patients were classified into three groups based on implant programming: pre-guideline (PS), post-guideline and guideline compliant (GC) and post-guideline but not guideline compliant (NGC). The end-points were the first occurrence of any device therapy (ATP or shock), ICD shock, syncope and all-cause mortality. Survival analysis was used to evaluate outcomes. RESULTS: 1003 patients were included (mean follow-up 1519 ± 1005 days). In primary prevention patients (n = 583) freedom from ICD therapy (91.5% vs. 73.6%, p < .001) or shock (94.7% vs 84.8%, p = .02) were significantly higher in GC compared to PS patients, without significant increase in syncope or mortality. In secondary prevention patients (n = 420) freedom from any ICD therapy or any shock were non-significantly higher in GC compared to PS patients, without an increase in syncope or mortality. CONCLUSIONS: In primary prevention patients a standardized programming protocol, incorporating generic programming, reduced the burden of ICD therapy without an increase in adverse outcomes.

The extravascular implantable cardioverter-defibrillator: The pivotal study plan.

BACKGROUND: Transvenous implantable cardioverter defibrillators (TV ICD) provide life-saving therapy for millions of patients worldwide. However, they are susceptible to several potential short- and long- term complications including cardiac perforation and pneumothorax, lead dislodgement, venous obstruction, and infection. The extravascular ICD system's novel design and substernal implant approach avoids the risks associated with TV ICDs while still providing pacing features and similar generator size to TV ICDs. STUDY DESIGN: The EV ICD pivotal study is a prospective, multicenter, single-arm, nonrandomized, premarket clinical study designed to examine the safety and acute efficacy of the system. This study will enroll up to 400 patients with a Class I or IIa indication for implantation of an ICD. Implanted subjects will be followed up to approximately 3.5 years, depending on when the patient is enrolled. OBJECTIVE: The clinical trial is designed to demonstrate safety and effectiveness of the EV ICD system in human use. The safety endpoint is freedom from major complications, while the efficacy endpoint is defibrillation success. Both endpoints will be assessed against prespecified criteria. Additionally, this study will evaluate antitachycardia pacing performance, electrical performance, extracardiac pacing sensation, asystole pacing, appropriate and inappropriate shocks, as well as a summary of adverse events. CONCLUSION: The EV ICD pivotal study is designed to provide clear evidence addressing the safety and efficacy performance of the EV ICD System.

The Impact of Vendor-Specific Ultrasound Beam-Forming and Processing Techniques on the Visualization of In Vitro Experimental "Scar": Implications for Myocardial Scar Imaging Using Two-Dimensional and Three-Dimensional Echocardiography.

BACKGROUND: Myocardial scar appears brighter compared with normal myocardium on echocardiography because of differences in tissue characteristics. The aim of this study was to test how different ultrasound pulse characteristics affect the brightness contrast (i.e., contrast ratio [CR]) between tissues of different acoustic properties, as well as the accuracy of assessing tissue volume. METHODS: An experimental in vitro "scar" model was created using overheated and raw pieces of commercially available bovine muscle. Two-dimensional and three-dimensional ultrasound scanning of the model was performed using combinations of ultrasound pulse characteristics: ultrasound frequency, harmonics, pulse amplitude, steady pulse (SP) emission, power modulation (PM), and pulse inversion modalities. RESULTS: On both two-dimensional and three-dimensional imaging, the CR between the "scar" and its adjacent tissue was higher when PM was used. PM, as well as SP ultrasound imaging, provided good "scar" volume quantification. When tested on 10 "scars" of different size and shape, PM resulted in lower bias (-9.7 vs 54.2 mm3) and narrower limits of agreement (-168.6 to 149.2 mm3 vs -296.0 to 404.4 mm3, P = .03). The interobserver variability for "scar" volume was better with PM (intraclass correlation coefficient = 0.901 vs 0.815). Two-dimensional and three-dimensional echocardiography with PM and SP was performed on 15 individuals with myocardial scar secondary to infarction. The CR was higher on PM imaging. Using cardiac magnetic resonance as a reference, quantification of myocardial scar volume showed better agreement when PM was used (bias, -645 mm3; limits of agreement, -3,158 to 1,868 mm3) as opposed to SP (bias, -1,138 mm3; limits of agreement, -5,510 to 3,233 mm3). CONCLUSIONS: The PM modality increased the CR between tissues with different acoustic properties in an experimental in vitro "scar" model while allowing accurate quantification of "scar" volume. By applying the in vitro findings to humans, PM resulted in higher CR between scarred and healthy myocardium, providing better scar volume quantification than SP compared with cardiac magnetic resonance.