Cardiovascular Devices Research Articles

Update on Cardiovascular Implantable Electronic Device Infections and Their Prevention, Diagnosis, and Management: A Scientific Statement From the American Heart Association: Endorsed by the International Society for Cardiovascular Infectious Diseases.

The American Heart Association sponsored the first iteration of a scientific statement that addressed all aspects of cardiovascular implantable electronic device infection in 2010. Major advances in the prevention, diagnosis, and management of these infections have occurred since then, necessitating a scientific statement update. An 11-member writing group was identified and included recognized experts in cardiology and infectious diseases, with a career focus on cardiovascular infections. The group initially met in October 2022 to develop a scientific statement that was drafted with front-line clinicians in mind and focused on providing updated clinical information to enhance outcomes of patients with cardiovascular implantable electronic device infection. The current scientific statement highlights recent advances in prevention, diagnosis, and management, and how they may be incorporated in the complex care of patients with cardiovascular implantable electronic device infection.

Biofunctionalization of surfaces to minimize undesirable effects in cardiovascular assistance devices.

The reactivity of blood with non-endothelial surface is a challenge for long-term Ventricular Assist Devices development, usually made with pure titanium, which despite of being inert, low density and high mechanical resistance it does not avoid the thrombogenic responses. Here we tested a modification on the titanium surface with Laser Induced Periodic Surface Structures followed by Diamond Like Carbon (DLC) coating in different thicknesses to customize the wettability profile by changing the surface energy of the titanium. Four different surfaces were proposed: (1) Pure Titanium as Reference Material (RM), (2) Textured as Test Sample (TS), (3) Textured with DLC 0.3μm as (TSA) and (4) Textured with 2.4μm DLC as (TSB). A single implant was positioned in the abdominal aorta of Wistar rats and the effects of hemodynamic interaction were evaluated without anticoagulant drugs. After twelve weeks, the implants were extracted and subjected to qualitative analysis by Scanning Electron Microscopy under low vacuum and X-ray Energy Dispersion. The regions that remained in contact with the wall of the aorta showed encapsulation of the endothelial tissue. TSB implants, although superhydrophilic, have proven that the DLC coating inhibits the adhesion of biological material, prevents abrasive wear and delamination, as observed in the TS and TSA implants. Pseudo- neointimal layers were heterogeneously identified in higher concentration on Test Surfaces.

Managing ventricular arrhythmias and implantable cardiac defibrillator shocks after left ventricular assist device implantation.

Continuous flow left ventricular assist devices (CF-LVADs) have been shown to reduce mortality and morbidity in patients with advanced heart failure with reduced ejection fraction. However, ventricular arrhythmias (VA) are common, are mostly secondary to underlying myocardial scar, and have a higher incidence in patients with pre-LVAD VA. Sustained VA is well tolerated in the LVAD patient but can result in implantable defibrillator (ICD) shocks, right ventricular failure, hospitalizations, and reduced quality of life. There is limited data regarding best practices for the medical management of VA as well as the role for procedural interventions in patients with uncontrolled VA and/or ICD shocks. Vast majority of CF-LVAD patients have a preexisting cardiovascular implantable electronic device (CIED) and ICD and/or cardiac resynchronization therapies are continued in many. Several questions, however, remain regarding the efficacy of ICD and CRT following CF-LVAD. Moreover, optimal CIED programming after CF-LVAD implantation. Therefore, the primary objective of this review article is to provide the most up-to-date evidence and to provide guidance on the clinical significance, pathogenesis, predictors, and management strategies for VA and ICD therapies in the CF-LVAD population. We also discuss knowledge gaps as well as areas for future research.

A Patient-Centered Intervention Reduces Disparities in Remote Monitoring in Patients With Implanted Cardiac Devices

BackgroundRemote monitoring (RM) is recommended for patients with cardiovascular implantable electronic devices, yet many individuals, especially those living in underserved communities, fail to receive this guideline-directed care. Multilevel interventions that target patient and clinic-level barriers to RM care may be beneficial. ObjectivesThis study sought to evaluate a remotely delivered, patient-centered intervention to improve RM activation and adherence and reduce disparities in RM care. MethodsThe intervention provides home delivery of remote monitor, phone-based education, monitor setup, and facilitation of first transmission. A retrospective cohort analysis was performed using RM data from 190,643 patients (71.6 ± 12.7 years of age, 40.5% female) implanted with a pacemaker or defibrillator at 4,195 U.S. clinics between October 2015 and October 2019. Outcomes included RM activation (12 weeks and 1-year postimplantation) and adherence to clinic-scheduled transmissions. Patients receiving a cardiovascular implantable electronic deviceimplant 0 to 730 days before (control group, n = 95,861) and after (intervention group, n = 94,782) intervention launch were compared using logistic regression and generalized estimating equations. Multivariable models included patient, clinic, and neighborhood socioeconomic characteristics. ResultsThe odds of achieving guideline-recommended activation were significantly higher in the intervention group at 12 weeks (OR: 2.99; 76.7% vs 60.9%; P < 0.001) and 1 year (OR: 3.05; 88.2% vs 79.3%; P < 0.001). Adherence to scheduled transmissions was also higher in the intervention group compared with the control group (OR: 2.18; 89.1% vs 81.9%; P < 0.001). Preintervention disparities in RM activation and adherence were reduced in underserved groups following the intervention. ConclusionsA remotely delivered patient-centered intervention was associated with earlier activation and improved adherence to RM while reducing disparities in RM care.

Barriers and Facilitators Associated With Remote Monitoring Adherence Among Veterans With Pacemakers and Implantable Cardioverter-Defibrillators: Qualitative Cross-Sectional Study.

The Heart Rhythm Society strongly recommends remote monitoring (RM) of cardiovascular implantable electronic devices (CIEDs) because of the clinical outcome benefits to patients. However, many patients do not adhere to RM and, thus, do not achieve these benefits. There has been limited study of patient-level barriers and facilitators to RM adherence; understanding patient perspectives is essential to developing solutions to improve adherence. We sought to identify barriers and facilitators associated with adherence to RM among veterans with CIEDs followed by the Veterans Health Administration. We interviewed 40 veterans with CIEDs regarding their experiences with RM. Veterans were stratified into 3 groups based on their adherence to scheduled RM transmissions over the past 2 years: 6 fully adherent (≥95%), 25 partially adherent (≥65% but <95%), and 9 nonadherent (<65%). As the focus was to understand challenges with RM adherence, partially adherent and nonadherent veterans were preferentially weighted for selection. Veterans were mailed a letter stating they would be called to understand their experiences and perspectives of RM and possible barriers, and then contacted beginning 1 week after the letter was mailed. Interviews were structured (some questions allowing for open-ended responses to dive deeper into themes) and focused on 4 predetermined domains: knowledge of RM, satisfaction with RM, reasons for nonadherence, and preferences for health care engagement. Of the 44 veterans contacted, 40 (91%) agreed to participate. The mean veteran age was 75.3 (SD 7.6) years, and 98% (39/40) were men. Veterans had been implanted with their current CIED for an average of 4.4 (SD 2.8) years. A total of 58% (23/40) of veterans recalled a discussion of home monitoring, and 45% (18/40) reported a good understanding of RM; however, when asked to describe RM, their understanding was sometimes incomplete or not correct. Among the 31 fully or partially adherent veterans, nearly all were satisfied with RM. Approximately one-third recalled ever being told the results of a remote transmission. Among partially or nonadherent veterans, only one-fourth reported being contacted by a Department of Veterans Affairs health care professional regarding not having sent a remote transmission; among those who had troubleshooted to ensure they could send remote transmissions, they often relied on the CIED manufacturer for help (this experience was nearly always positive). Most nonadherent veterans felt more comfortable engaging in RM if they received more information or education. Most veterans were interested in being notified of a successful remote transmission and learning the results of their remote transmissions. Veterans with CIEDs often had limited knowledge about RM and did not recall being contacted about nonadherence. When they were contacted and troubleshooted, the experience was positive. These findings provide opportunities to optimize strategies for educating and engaging patients in RM.

Generation of synthetic aortic valve stenosis geometries for in silico trials.

In silico trials are a promising way to increase the efficiency of the development, and the time to market of cardiovascular implantable devices. The development of transcatheter aortic valve implantation (TAVI) devices, could benefit from in silico trials to overcome frequently occurring complications such as paravalvular leakage and conduction problems. To be able to perform in silico TAVI trials virtual cohorts of TAVI patients are required. In a virtual cohort, individual patients are represented by computer models that usually require patient-specific aortic valve geometries. This study aimed to develop a virtual cohort generator that generates anatomically plausible, synthetic aortic valve stenosis geometries for in silico TAVI trials and allows for the selection of specific anatomical features that influence the occurrence of complications. To build the generator, a combination of non-parametrical statistical shape modeling and sampling from a copula distribution was used. The developed virtual cohort generator successfully generated synthetic aortic valve stenosis geometries that are comparable with a real cohort, and therefore, are considered as being anatomically plausible. Furthermore, we were able to select specific anatomical features with a sensitivity of around 90%. The virtual cohort generator has the potential to be used by TAVI manufacturers to test their devices. Future work will involve including calcifications to the synthetic geometries, and applying high-fidelity fluid-structure-interaction models to perform in silico trials.

Cost-effectiveness of remote monitoring for cardiac implantable electronic devices compared with conventional follow-up: a systematic review

Abstract Background Remote monitoring (RM) of cardiovascular implantable electronic devices (CIEDs) is a form of virtual patient care that involves electronic transmission of CIED diagnostics and remote assessment of this information by clinic staff. Despite expert recommendations advocating its use, adoption remains modest due to inconsistent funding policies across health systems. Purpose This study aims to identify and synthesize existing literature in the cost-effectiveness of RM compared with in-person clinic assessments alone in patients with CIEDs. Methods We conducted a systematic review of available economic evaluations (including cost-effectiveness, cost-utility, cost-consequence analyses) and costing analyses (which examines costs but not clinical benefits) of RM following CIED implantation compared to in-person clinic follow-up alone. Study outcomes included incremental costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Results Of the 1151 unique citations, a total of 27 studies were included. The studies were from Europe (n=20), USA (n=5), or Canada (n=2). Remote transmissions, when detailed in the study, were predominantly patient- and/or physician- triggered, but some also included automatic home monitor transmissions. Fourteen studies (52%) were costing analyses, and the remaining 13 studies were economic evaluations. The majority of studies (78%; n=21) reported cost-savings associated with RM compared to in-clinic follow up alone. Of the 13 economic evaluations, there were 6 cost-utility analyses, which all reported that RM provided additional QALYs for additional costs that met country-specific thresholds for good value in health care. Studies varied greatly in the costs considered, the outcomes measured, and the time horizons used. Conclusion Remote monitoring of patients with CIEDs was associated with cost-savings in most studies and across different healthcare systems. RM may be considered cost-effective when conventional thresholds for good value in health care are adopted. Despite heterogeneity in methods of economic evaluation in the studies included, the overall data in this systematic review supports greater implementation of RM technology to improve health system costs and efficiency.

A predictors for 10-year mortality and clinical events in patients with chronic coronary total occlusion lesion

Abstract Background Despite advances in cardiovascular intervention techniques and devices, the treatment of patients with chronic coronary total occlusion CTO lesions is challenging yet. We evaluated predictors of 10-year mortality and clinical events in patients with CTO lesions in this study. Methods This study is a single-center, prospective, all-comer registry designed to reflect "real world" practice since 2001. Of a total of 1,672 consecutive patients were diagnosed with CTO lesions by coronary angiogram. The primary endpoints were all-cause death or major adverse cerebral, and cardiac events (MACCE) defined as the composite of all-cause death, myocardial infarction (MI), any coronary revascularization, and stroke up to 10 years. We derived for final results, from survival analysis by Kaplan-Meier and Cox-proportional regression analysis. Results In this study, males were 1,255 (75.1%), and the mean age was 65.2±10.9. Also, a total of 660 patients had received a successful PCI for CTO lesions at enrollment. A total of 267 patients was heart failure. Ten years of clinical follow, MACCE occurs in 407 cases (56.6%), all-cause death in 152 cases (18.5%), cardiac death in 87 cases (9.9%), myocardial infarction (MI) in 54 cases (7.7%), any revascularization of 251 cases (30.7%), and stroke of 41 cases (6.3%) by Kaplan-Meier analysis. In a multiple Cox-proportional regression analysis, a prior myocardial infarction, reduced LV ejection fraction less than 50%, chronic kidney disease, multi-vessel disease had increased a risk of MACCE and the use of statin, and aspirin had reduced a risk of MACCE. Also, an aging, prior MI, reduced LV ejection fraction less than 40%, and multi-vessel disease had increased a risk of all-cause death and the use of statin, and renin-angiotensin system inhibitors, nitrates, statin, and aspirin had reduced a risk of risk of all-cause death. However, PCI for CTO lesions could not reduce both of MACCE and all-cause death. Conclusions The study found that a prior myocardial infarction, reduced LV ejection fraction, chronic kidney disease, and multi-vessel disease were associated with an increased risk of MACCE, while the use of statins and aspirin reduced the risk of MACCE. Furthermore, PCI for CTO lesions did not reduce the incidence of MACCE or all-cause death. These findings highlight the need for further research and development of more effective treatment strategies for patients with CTO lesions.

Strategies to enhance remote monitoring adherence among patients with cardiovascular implantable electronic devices

Remote monitoring (RM) of patients with cardiovascular implantable electronic devices (CIEDs) (pacemakers and implantable cardioverter-defibrillators) has a Class 1, Level of Evidence A Heart Rhythm Society recommendation. Yet RM adherence varies widely across settings, and factors associated with variation are not understood. The purpose of this study was to identify strategies for supporting RM across Veterans Health Administration (VHA) facilities. In a national evaluation, we surveyed and interviewed 27 nurses, medical instrument technicians, and advanced practice providers across 26 VHA facilities (following approximately 15,000 CIED patients). Participants were selected based on overall patient adherence by facility, which ranged from 46%-96%. Questions covered RM adherence strategies, manufacturer resources, organizational characteristics, and workflows for optimizing adherence. All clinicians reported that RM adherence was extremely important (53.8%), very important (34.6%), or important (11.5%) for improving patient outcomes. High performing facilities prioritized consistent patient education about RM and evaluated nonadherence using dashboards and manufacturer web sites. High performing facilities instituted clear standard operating procedures that defined staff responsibilities and facilitated efficient contact with nonadherent patients and then family members by phone and then mail. Clinicians based at high performing facilities spent twice as many hours per week (9.1) on average managing RM adherence compared to other facilities (4.5). Effective communication (internally and with non-VHA care partners) and use of CIED manufacturer resources were essential. Facilities that were not high performing rarely used these strategies. Clinicians can support high RM adherence by emphasizing patient education, regularly assessing and addressing nonadherence using staff protocols, and engaging CIED manufacturers.

Poly (Lactic Acid) Applications in Biomedical Engineering

Medical devices like implants are playing a pivotal role in medicine. As a polyester, Polylactic acid (PLA) and its copolymers are widely used in the medical area. They are used in several sections including cardiovascular and orthopedic devices, as well as advanced technologies of tissue engineering and drug delivery. In this paper, cardiovascular devices including applications of PLLA coating as drug delivery system and BVS material are introduced. Specifically, PLA can be used to foster scaffolds for bone tissue and cardiovascular tissue engineering. Then this paper introduces PLA applied in the form of nanoparticles and micelles in drug delivery. The special degrading process makes PLA an active drug delivery carrier. And it could also be used to produce biodegradable orthopaedic operation devices and offer the advantage of being free from taking out of the human body. Processing techniques are pivotal prerequisites of applications of medical usage, like electrospun fibers are used in cardiovascular and drug delivery applications. The paper summarizes the use of PLA material in those areas, and foresees the future for a prediction of the attractive prospect. Although the applications are faced with limitations like mechanical properties now, they still have a promising future in biomedicine.

Abstract 12875: Echocardiographic Findings Associated With Subsequent Risk of Native Valve Endocarditis

Introduction: The association of echocardiographic measurements and subsequent risk of left-sided native valve endocarditis (LS-NVE) is undefined. Aim: To determine if transthoracic echocardiographic (TTE) measurements are associated with the subsequent development of LS-NVE in patients without recognized cardiac predisposing conditions. Methods: Institutional databases were evaluated for adults diagnosed with LS-NVE from 2008 to 2020. Patients with prosthetic valves, cardiovascular implantable electronic devices, intracardiac devices, injection drug use, and recognized predisposing cardiac conditions were excluded. Patients with a TTE performed 6 months to 3 years before developing LS-NVE were included as cases. Controls were patients within the same Mayo Clinic location with a TTE report and were matched in a 1:3 ratio according to age, gender, Charlson Comorbidity Index (CCI), and echocardiography date. Multivariate logistic-regression analyses adjusting significant variables between cohort's were performed. A p-value &lt;0.05 was considered significant. Results: There were 148 cases and 431 matched controls. The median age was 63.8 (IQR: 53.6 - 74.6) years, and 329 (56.8%) patients were males. LS-NVE cases had a higher prevalence of diabetes mellitus (46.6% vs. 30.4%) and chronic kidney disease (46.6% vs. 28.1%) when compared with controls (p&lt;0.001 both). The median CCI score was 3 (IQR: 0-6) for cases and 2 (IQR: 0-6) for controls. After performing adjusted analyses, left ventricular outflow tract velocity (p=0.017), left ventricular ejection fraction (p=0.018), and E: e’ ratio (p=0.050) were associated with the development of LS-NVE ( Figure 1) . Conclusions: Echocardiographic measurements were associated with subsequent LS-NVE development in this preliminary investigation. A larger cohort of LS-NVE patients is needed to validate these findings.

Abstract 15795: Outcomes After Cardiac Implantable Electronic Devices Among People With and Without HIV

Introduction: The long-term outcomes of cardiovascular implantable electronic devices (CIED) in people with HIV (PWH) is unknown despite higher rates of sudden cardiac death and heart failure in HIV. Objective To compare outcomes between PWH and the general population who have CIEDs. Methods: Retrospective cohort study of patients receiving care at two academic hospitals in San Francisco who got CIEDs (pacemaker, implantable cardioverter defibrillator, cardiac resynchronization therapy ± defibrillator) from 2000-2018. Since CIEDs were rarer in PWH than in those without HIV, we also did a nested case-control study. Case and controls were matched by age, sex, and CIED type. Death data was obtained from the National Death Index. Results: We identified 3,268 patients who got CIEDs; 1% was PWH. In PWH at CIED implantation, mean HIV duration was 19 years, mean CD4 count was 449 cells/uL, 78% had undetectable viral loads, and all were on antiretroviral therapy. PWH were younger than the control (mean age 62 vs. 69 years, p &lt; 0.01). Both groups had similar rates of hypertension, diabetes, CAD, smoking, and drug use, but more PWH had hepatitis C than the control (25% vs. 3.0%, p &lt; 0.01). Both groups had a similar number of pacemakers (56% vs. 58%, p = 0.86) and defibrillators (44% vs. 39%, p = 0.56). Post-procedure, five (16%) PWH had lead failure or infection while nine (14%) controls had lead failure. One PWH with site infection reported IV drug use. Post CIED placement, median survival in years was 5.3 in PWH vs. 6.4 in controls. No strong association between HIV status and survival (HR 1.9 [95% CI 0.7 to 5.0]) was seen ( F igure ). Conclusions: To our knowledge, this is the first study looking at survival post CIED between PWH and the general population. Our findings suggest that the number of PWH getting CIEDs remains low despite no definitive evidence of procedural complications; and that PWH have similar survival to those without HIV. More studies exploring barriers to CIED placement in PWH are needed.

Abstract 14907: Trends in Management Practices of Cardiovascular Implantable Electronic Device Infections in Patients With End-Stage Kidney Disease

Introduction: End-stage kidney disease (ESKD) patients with cardiovascular implantable electronic devices (CIEDs) are at higher risk of bloodstream infection. While prior studies have shown high procedural success rates of lead extraction and improved outcomes, the rates of lead extraction in these patients at the national level are not known. Aim: To evaluate trends in management practices of CIED infections in ESKD patients. Methods: Utilizing the United States Renal Data System and ICD 9 codes, we identified patients aged &gt;18 years with ESKD on hemodialysis who underwent first CIED implant from January 2006-September 2014. For study purposes we studied management strategy in those who developed CIED infection within 1 year of device implant. We excluded patients with a prosthetic valve as the ICD 9 code for CIED infection also includes prosthetic valve infection. We restricted the study population to those with CIED implanted until September 2014 as ICD 10 codes were implemented in September 2015 and the ICD 10 code is not specific code for CIED infection (it also includes vascular device infections). After identifying patients diagnosed with CIED infection, we utilized procedure codes for lead extraction within 60 days of the infection diagnosis to determine the mode of management. In the absence of procedure codes for extraction, patients were presumed to have been managed medically. Results: A total of 380 ESKD patients undergoing CIED implant from 2006-2014 were diagnosed with CIED infections within 1 year of device implant. Of these, 183 (48.16%) patients underwent lead extraction within 60 days. When analyzed by year, the rates of utilization of lead extraction in these patients have not changed significantly from 2006 to 2015 (Table). Conclusions: The utilization of lead extraction for management of CIED infections in ESKD patients remains low (~50%). This data calls for a reassessment of management strategy for device infections in ESKD patients.

Synthesizing a multifunctional polymer to construct the catalytically NO-generating coating for improving corrosion resistance and biocompatibility of the magnesium alloy stent materials

Owing to its excellent mechanical properties and biodegradability, magnesium-based alloys have become the research focus of biodegradable cardiovascular materials. However, the in vivo rapid degradation and poor surface endothelial regeneration and repair ability still restrict their clinical applications in the field of vascular stent materials. Nitric oxide (NO), as an endogenous gas signaling molecule, has multiple effects such as anticoagulation, promoting endothelialization, and anti-restenosis, showing a great potential for improving the performances of the cardiovascular materials and devices. In the present study, based on six-arm polyethylene glycol (PEG), a novel anticoagulant polymer (PEG-Hep-SeCA) with the catalytic release of NO was synthesized by successively introducing heparin and selenocystamine, followed by the immobilization of the as-synthesized polymer on the Zn2+-loaded polydopamine coating modified magnesium alloy surface to enhance the anti-corrosion and biocompatibility. The results demonstrated that the PEG-Hep-SeCA polymer coating was uniform and dense, which could not only obviously enhance the anticorrosion and the hydrophilicity of the magnesium alloy, but also selectively promote the bovine serum albumin (BSA) adsorption, thereby significantly improving the endothelial cells (ECs) growth and hemocompatibility. Additionally, the as-prepared polymer coating could effectively catalyze the release of NO from endogenous NO donors, which can further ameliorate the hemocompatibility and ECs growth, as well as enhance the expression of vascular endothelial cell growth factor (VEGF) and NO of the ECs. Therefore, this study opens a new way to construct the multifunctional coating with the ability of catalytic releasing NO on the surfaces of the magnesium-based alloys to simultaneously reduce the corrosion speed, improve the hemocompatibility, and accelerate the reendothelialization.

Regulatory Oversight of Cardiovascular Devices—Why We Care

Regulatory Oversight of Cardiovascular Devices—Why We Care

Aligning US Agency Policies for Cardiovascular Devices Through the Breakthrough Devices Program

The US Food and Drug Administration (FDA) and Centers for Medicare & Medicaid Services (CMS) have different statutory authorities; FDA evaluates safety and effectiveness for market authorization of medical devices while CMS determines whether coverage is "reasonable and necessary" for its beneficiaries. CMS has recently enacted policies automatically providing supplemental reimbursement for new, costly devices authorized after designation in FDA's Breakthrough Devices Program (BDP) and in June 2023 issued notice for a new Transitional Coverage for Emerging Technologies pathway, accelerating coverage for Breakthrough devices. Aiming to incentivize innovation, FDA awards Breakthrough designations early in device development to expedite market authorization and can accept greater uncertainty in benefit and risk, contingent on postmarket evidence generation. Since 2020, Breakthrough designation has effectively automatically qualified devices to receive supplemental Medicare reimbursement after CMS waived a long-standing requirement that devices demonstrate "substantial clinical improvement" for beneficiaries. Using publicly available information, 3 examples of cardiovascular devices illustrate that the BDP may allow for FDA authorization based on less rigorous evidence, such as single-arm trials focused on surrogate end points with short-term follow-up whose participants are often not representative of Medicare beneficiaries. In 1 case, Breakthrough designation allowed a 30% decrease in enrollment of a trial used to support approval. Initial positive findings for some devices have remained unverified, and in 1 case even partially nullified, by postmarket studies. Manufacturers have also used Breakthrough designations to set the price of devices to facilitate additional pass-through payments, leading to higher short-term and long-term costs to CMS and health care systems. The BDP may qualify new, costly devices for higher and automatic Medicare reimbursement despite evidence not being representative of CMS beneficiaries and persistent uncertainty of benefit and risk. To ensure the best evidence is generated to inform clinical care, FDA could apply more selectivity to BDP eligibility, specify objective criteria for revoking Breakthrough designation when appropriate, and ensure timely postmarket evidence generation, whereas CMS could independently review clinical evidence, advise manufacturers about standards for coverage review, and make supplemental payments and long-term device reimbursement contingent on clinical outcome benefit and postmarket evidence generation.

Imaging in patients with cardiovascular implantable electronic devices: part 1-imaging before and during device implantation. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association (EHRA) of the ESC.

More than 500 000 cardiovascular implantable electronic devices (CIEDs) are implanted in the European Society of Cardiology countries each year. The role of cardiovascular imaging in patients being considered for CIED is distinctly different from imaging in CIED recipients. In the former group, imaging can help identify specific or potentially reversible causes of heart block, the underlying tissue characteristics associated with malignant arrhythmias, and the mechanical consequences of conduction delays and can also aid challenging lead placements. On the other hand, cardiovascular imaging is required in CIED recipients for standard indications and to assess the response to device implantation, to diagnose immediate and delayed complications after implantation, and to guide device optimization. The present clinical consensus statement (Part 1) from the European Association of Cardiovascular Imaging, in collaboration with the European Heart Rhythm Association, provides comprehensive, up-to-date, and evidence-based guidance to cardiologists, cardiac imagers, and pacing specialists regarding the use of imaging in patients undergoing implantation of conventional pacemakers, cardioverter defibrillators, and resynchronization therapy devices. The document summarizes the existing evidence regarding the use of imaging in patient selection and during the implantation procedure and also underlines gaps in evidence in the field. The role of imaging after CIED implantation is discussed in the second document (Part 2).

Imaging in patients with cardiovascular implantable electronic devices: part 2-imaging after device implantation. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association (EHRA) of the ESC.

Cardiac implantable electronic devices (CIEDs) improve quality of life and prolong survival, but there are additional considerations for cardiovascular imaging after implantation-both for standard indications and for diagnosing and guiding management of device-related complications. This clinical consensus statement (part 2) from the European Association of Cardiovascular Imaging, in collaboration with the European Heart Rhythm Association, provides comprehensive, up-to-date, and evidence-based guidance to cardiologists, cardiac imagers, and pacing specialists regarding the use of imaging in patients after implantation of conventional pacemakers, cardioverter defibrillators, and cardiac resynchronization therapy (CRT) devices. The document summarizes the existing evidence regarding the role and optimal use of various cardiac imaging modalities in patients with suspected CIED-related complications and also discusses CRT optimization, the safety of magnetic resonance imaging in CIED carriers, and describes the role of chest radiography in assessing CIED type, position, and complications. The role of imaging before and during CIED implantation is discussed in a companion document (part 1).

Structural Identification of Zotarolimus (ABT-578) Metabolites Generated by Human Liver Microsomes Using Ion-Trap and High-Resolution Time-of-Flight Mass Spectrometry in Combination with the Analysis of Fragmentation Patterns.

Zotarolimus (ABT-578) is a sirolimus derivative that, like sirolimus and everolimus, is an inhibitor of cell growth via inhibition of the mechanistic target of rapamycin (mTOR). Zotarolimus was developed for coating coronary stents to prevent smooth muscle cell proliferation and restenosis. Albeit zotarolimus-eluting cardiovascular devices have been on the market for years, details of zotarolimus drug metabolism in humans are still unknown. Hence, it was the goal of the present study to identify zotarolimus metabolites generated by incubation with human liver microsomes. Metabolite structures were identified using high-resolution mass spectrometry, MS/ion-trap (MSn), and comparison of fragmentation patterns of the metabolites with those of zotarolimus and other known sirolimus derivatives. Kinetic parameters such as incubation time, human liver microsomal protein concentrations, and drug concentrations were optimized before scaling up the metabolism experiments. Human liver microsomes mainly hydroxylated and/or demethylated zotarolimus. The structures of the following metabolites were identified: O-demethylated metabolites: 39-O-desmethyl, 16-O-desmethyl, and 27-O-desmethyl zotarolimus; hydroxylated metabolites: hydroxy piperidine zotarolimus, 11-hydroxy, 12-hydroxy, 14-hydroxy, 23-hydroxy, 24-hydroxy, 25-hydroxy, 45/46-hydroxy, and 49-hydroxy zotarolimus; demethylated-hydroxylated metabolites: 16-O-desmethyl, 23/24-hydroxy; 39-O-desmethyl, 23/24-hydroxy; 39-O-desmethyl, 25-hydroxy zotarolimus; 39-O-desmethyl, 11-hydroxy zotarolimus; 39-O-desmethyl, hydroxy-piperidine zotarolimus; 27-O-desmethyl, 45/46-hydroxy zotarolimus; didemethylated metabolites: 16,39-O-didesmethyl zotarolimus; 16,27-O-didesmethyl zotarolimus; 27,39-O-didesmethyl zotarolimus; and dihydroxylated metabolites: 11,24-dihydroxy zotarolimus, 12,24-dihydroxy zotarolimus, and 11,47/48-dihydroxy zotarolimus. It is concluded that zotarolimus is extensively metabolized by human liver microsomes. Twenty-four of these metabolites could be structurally identified using a combination of ion-trap MSn and high-resolution mass spectrometry.

Lead Extraction and Mortality Among Patients With Cardiac Implanted Electronic Device Infection

Complete hardware removal is a class I recommendation for cardiovascular implantable electronic device (CIED) infection, but practice patterns and outcomes remain unknown. To quantify the number of Medicare patients with CIED infections who underwent implantation from 2006 to 2019 and lead extraction from 2007 to 2019 to analyze the outcomes in these patients in a nationwide clinical practice cohort. This cohort study included fee-for-service Medicare Part D beneficiaries from January 1, 2006, to December 31, 2019, who had a de novo CIED implantation and a CIED infection more than 1 year after implantation. Data were analyzed from January 1, 2005, to December 31, 2019. A CIED infection, defined as (1) endocarditis or infection of a device implant and (2) documented antibiotic therapy. The primary outcomes of interest were device infection, device extraction, and all-cause mortality. Time-varying multivariable Cox proportional hazards regression models were used to evaluate the association between extraction and survival. Among 1 065 549 patients (median age, 78.0 years [IQR, 72.0-84.0 years]; 50.9% male), mean (SD) follow-up was 4.6 (2.9) years after implantation. There were 11 304 patients (1.1%) with CIED infection (median age, 75.0 years [IQR, 67.0-82.0 years]); 60.1% were male, and 7724 (68.3%) had diabetes. A total of 2102 patients with CIED infection (18.6%) underwent extraction within 30 days of diagnosis. Infection occurred a mean (SD) of 3.7 (2.4) years after implantation, and 1-year survival was 68.3%. There was evidence of highly selective treatment, as most patients did not have extraction within 30 days of diagnosed infection (9202 [81.4%]), while 1511 (13.4%) had extraction within 6 days of diagnosis and 591 (5.2%) had extraction between days 7 and 30. Any extraction was associated with lower mortality compared with no extraction (adjusted hazard ratio [AHR], 0.82; 95% CI, 0.74-0.90; P < .001). Extraction within 6 days was associated with even lower risk of mortality (AHR, 0.69; 95% CI, 0.61-0.78; P < .001). In this study, a minority of patients with CIED infection underwent extraction. Extraction was associated with a lower risk of death compared with no extraction. The findings suggest a need to improve adherence to guideline-directed care among patients with CIED infection.