Evaluation of cardiovascular implantable electronic device leads post implant: ElectroPhysiology Predictable And SuStainable Implementation Of National Registries (EP PASSION).

Post-market evaluation is important to ensure the ongoing safety and effectiveness of cardiovascular implantable electronic device (CIED) leads. The Twenty-First Century Cures Act and subsequent Food and Drug Administrative (FDA) Guidance provide an opportunity to leverage real-world data sources for this purpose. The past 4 years have seen the development of EP PASSION: a multi-stakeholder, collaborative effort between the FDA, CIED manufacturers, Heart Rhythm Society, and academics. Using real-world data, EP PASSION enables longitudinal evaluation of the long-term safety of CIED leads, addressing limitations of current approaches to generate evidence that informs regulatory, clinical, and manufacturer decision-making. This state of the art article describes the impetus for and launch of EP PASSION, the lessons learned, its current state, the current analytic approach, and the strengths and limitations of leveraging extant data sources for post-market lead evaluation. We also compare EP PASSION to traditional post-approval studies and describe possible future directions.

Cardiovascular implantable electronic device lead safety: Harnessing real-world remote monitoring data for medical device evaluation.

BACKGROUND: Current methods to identify cardiovascular implantable electronic device lead failure include postapproval studies, which may be limited in scope, participant numbers, and attrition; studies relying on administrative codes, which lack specificity; and voluntary adverse event reporting, which cannot determine incidence or attribution to the lead. OBJECTIVE: The purpose of this study was to determine whether adjudicated remote monitoring (RM) data can address these limitations and augment lead safety evaluation. METHODS: Among 48,191 actively monitored patients with a cardiovascular implantable electronic device, we identified RM transmissions signifying incident lead abnormalities and, separately, identified all leads abandoned or extracted between April 1, 2019, and April 1, 2021. We queried electronic health record and Medicare fee-for-service claims data to determine whether patients had administrative codes for lead failure. We verified lead failure through manual electronic health record review. RESULTS: Of the 48,191 patients, 1170 (2.4%) had incident lead abnormalities detected by RM. Of these, 409 patients had administrative codes for lead failure, and 233 of these 409 patients (57.0%) had structural lead failure verified through chart review. Of the 761 patients without administrative codes, 167 (21.9%) had structural lead failure verified through chart review. Thus, 400 patients with RM transmissions suggestive of lead abnormalities (34.2%) had structural lead failure. In addition, 200 patients without preceding abnormal RM transmissions had leads abandoned or extracted for structural failure, making the total lead failure cohort 600 patients (66.7% with RM abnormalities, 33.3% without). Patients with isolated right atrial or left ventricular lead failure were less likely to have lead replacement and administrative codes reflective of lead failure. CONCLUSION: RM may strengthen real-world assessment of lead failure, particularly for leads where patients do not undergo replacement.

Initial Findings From the National Cardiovascular Data Registry of Atrial Fibrillation Ablation Procedures.

BACKGROUND: The National Cardiovascular Data Registry (NCDR) AFib Ablation Registry was created to assess real-world prevalence, demographic characteristics, procedural management, and outcomes of patients undergoing atrial fibrillation (AF) ablation procedures. OBJECTIVES: The goal of this study was to characterize the patient, hospital, and physician characteristics and in-hospital outcomes related to AF ablation in the first 5 years of the registry. METHODS: This paper describes the AFib Ablation Registry structure and governance, outcome assessment processes, data quality, and data collection processes. The characteristics of the patient population, hospitals, and in-hospital outcomes are also described. RESULTS: A total of 76,219 patients were included in the registry between January 2016 and December 2020 (mean age 65.5 ± 10.3 years, 65.2% male, 55.8% paroxysmal AF, mean CHA2DS2-VASc score 2.7 ± 1.6) treated by 708 physicians in 162 hospitals. Successful isolation of all pulmonary veins was achieved in 92.4% of patients. The prevalence of any complication during procedural admission was 2.50% and major complication was 0.9%, including significant bradycardia in 0.47%, heart failure in 0.47%, and pericardial effusion requiring intervention in 0.44%. Hospitalization >1 day occurred in 11.8% of patients, and in-hospital death was rare (n = 41 [0.05%]). CONCLUSIONS: The NCDR AFib Ablation Registry is the largest multicenter, prospective cohort study of patients undergoing catheter ablation worldwide. Results in the first 5 years showed that successful pulmonary vein isolation is achieved in the majority of patients, with a low rate of complications. Future studies from the registry will assess practice trends, evaluate treatment patterns associated with different patient outcomes, and support development of evidence-based guidelines.

An analysis of implantable cardiac device reliability. The case for improved postmarketing risk assessment and surveillance.

Implantable cardiac devices have become the mainstay of the treatment of patients with heart disease. However, data regarding their reliability and, inferentially, safety have been called into question. We reviewed annual reports submitted to the Food and Drug Administration Office of Device Evaluation by device manufacturers from 2003 to 2007. The annual number of implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy defibrillator (CRT-D) implants, explants, and returned devices were tabulated along with the cumulative (Cum) number of implants for each device. We derived an annual explantation rate (AER) defined as the ratio of the annual number of explants less the number of normal battery depletions/Cum (×1000). From 2003 to 2007, 256,392 CRT-D and 459,300 ICD devices were implanted in the United States. The overall mean (±SD) AERs for ICD and CRT-D devices were, respectively, 49.5 (15.6) per 1000 ICD devices and 82.6 (35.5) per 1000 CRT-D devices. The AER for each device type significantly decreased over the study period (P for trend <0.001) although the AER for CRT-D devices was 38% higher than that for ICD devices (P < 0.001). On average, 20.3% of CRT-D devices and 22.6% of ICD devices were returned to the manufacturer for analysis after explantation. The rates of explanted CRT-D and ICD devices decreased from 2003 to 2007. Notwithstanding this favorable trend, the AER for CRT-D devices was higher than that for ICD devices. Improved methods for tracking individual device histories are needed for more precise estimates of the risk of device explantation for suspected malfunction. The proportion of devices returned to the manufacturer is suboptimal and needs to be improved to better understand the mechanisms of device malfunction.

Electrophysiology devices and the regulatory approval process within the U.S. FDA and abroad.

Almost all electrophysiology (EP) devices need to obtain premarket approval before they can be commercially sold and available for use in the community. The US Food and Drug Administration (FDA) has different paths to market approval depending on the intended use and the associated risks of the device. The European Union and Japan have device approval processes that have many similarities as well as differences to the US regulatory system. This paper describes some of the history and background of the US device approval process with an emphasis on EP devices. It provides an overview of the different regulatory pathways in the USA that are currently being utilized and contrasts them to the procedures often used in the European Union and in Japan. It also touches on the impact of the twenty-first Century Cures Act and how the balance between premarket and postmarket regulatory oversight is continually being examined and refined.

A National Survey of Veterans Affairs Medical Centers' Cardiology Services.

A survey found that of cardiology services were widely available at facilities across the US Department of Veterans Affairs, but the types of services varied considerably based on facility complexity.

New technology in electrophysiology: FDA process and perspective.

The Food and Drug Administration (FDA) is a large regulatory agency that monitors everything from food, tobacco, and veterinary medicine to pharmaceutical drugs and medical devices. The Mission statement of the CDRH, one of the Centers of the FDA, in its most succinct form is to protect and promote public health. This is accomplished through timely and continued access to safe, effective, and high quality medical devices. This paper aims to review the overarching principles of the Agency's review process for cardiac devices as well as highlight some of the newer programs that FDA has engaged in to facilitate innovation, device development, research, and timely market approval.

Toward Sex-Specific Guidelines for Cardiac Resynchronization Therapy?

An important treatment for patients with heart failure is cardiac resynchronization therapy (CRT). Even though only 20% of women were included in clinical trials for CRT, a benefit has been shown in recent studies for subgroups of women compared to their male counterparts. Given this low inclusion rate of women in clinical studies, professional society guideline-based CRT recommendations, such as those by the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA)/Heart Rhythm Society (HRS), may not truly represent the best treatment for women, especially since most of the reports that showed this greater benefit in women were published after the latest guidelines. Despite having research and multiple publications regarding sex-specific heart failure outcomes and response to CRT, the ACCF/AHA/HRS guidelines have not yet been updated to account for the recent information regarding the differences in benefit for women and men with similar patient characteristics. This review discusses the physiology behind CRT, sex-specific characteristics of heart failure, and cardiac electrophysiology and summarizes the current sex-specific literature to encourage consideration of CRT guidelines for women and men separately.

The use of implantable cardioverter defibrillators for the prevention of sudden cardiac death: a review of the evidence and implications.

Sudden cardiac death (SCD) claims approximately 460,000 lives per year in the United States, and half of these deaths occur in people with a history of coronary artery disease. Patients with left ventricular dysfunction and a history of myocardial infarction are at especially high risk. There is now strong evidence from multiple well-designed randomized controlled trials that implantable cardioverter defibrillators (ICDs) save lives when used for both primary and secondary prevention. As indications for ICD implantation have broadened, considerable debate has taken place because of the substantial cost involved in widespread ICD utilization. This article summarizes the epidemiology of SCD, reviews the evidence supporting the use of ICDs in patients with ischemic cardiomyopathy, and explores some of the controversy surrounding ICD utilization that has arisen in the wake of recent trials that have utilized ICDs for the primary prevention of SCD.

Cardiac resynchronization therapy in women versus men: observational comparative effectiveness study from the National Cardiovascular Data Registry.

BACKGROUND: Women have been under-represented in trials of cardiac resynchronization therapy-defibrillators (CRT-D). Previous studies suggest that women benefit from CRT-D at shorter QRS duration than men and that there may be no benefit of CRT-D in patients without left bundle branch block (LBBB) regardless of patient sex. METHODS AND RESULTS: We compared sex-specific death risk in 75 079 patients with New York Heart Association class III or IV heart failure, reduced left ventricular ejection fraction, and prolonged QRS duration (≥120 ms) receiving either CRT-D or implantable cardioverter defibrillator in subgroups according to QRS morphology and 10-ms increments in QRS duration. We applied propensity score weighting to control for differences between treatments. Among patients with LBBB, women receiving CRT-D had a lower relative death risk than those receiving an implantable cardioverter-defibrillator (absolute difference, 11%; hazard ratio=0.74 [95% confidence interval, 0.68-0.81]). In men, the lower mortality with CRT-D versus implantable cardioverter defibrillator was less pronounced (absolute difference, 9%; hazard ratio=0.84 [0.79-0.89]; sex×device interaction P=0.025). In those without LBBB, the mortality difference was modest and did not differ between women and men (absolute difference, 3%; hazard ratio=0.88 [0.79-0.97] in women and absolute difference, 2%; hazard ratio=0.95 [0.91-0.998] in men; interaction P=0.17). In subgroups according to QRS duration, CRT-D was associated with better survival in both sexes with LBBB and QRS ≥130 ms, whereas there was no clear relation between QRS duration and survival in patients without LBBB regardless of patient sex. CONCLUSIONS: In a large real-world population CRT-D was associated with a lower mortality risk in both sexes with LBBB, although more pronounced among women. Only among those with LBBB, both sexes had better survival with longer QRS duration. The mortality differences in patients without LBBB were attenuated in both sexes.

Sex differences in device therapy for heart failure: utilization, outcomes, and adverse events.

BACKGROUND: Multiple studies of heart failure patients demonstrated significant improvement in exercise capacity, quality of life, cardiac left ventricular function, and survival from cardiac resynchronization therapy (CRT), but the underenrollment of women in these studies is notable. Etiological and pathophysiological differences may result in different outcomes in response to this treatment by sex. The observed disproportionate representation of women suggests that many women with heart failure either do not meet current clinical criteria to receive CRT in trials or are not properly recruited and maintained in these studies. METHODS: We performed a systematic literature review through May 2014 of clinical trials and registries of CRT use that stratified outcomes by sex or reported percent women included. One-hundred eighty-three studies contained sex-specific information. RESULTS: Ninety percent of the studies evaluated included ≤ 35% women. Fifty-six articles included effectiveness data that reported response with regard to specific outcome parameters. When compared with men, women exhibited more dramatic improvement in specific parameters. In the studies reporting hazard ratios for hospitalization or death, women generally had greater benefit from CRT. CONCLUSIONS: Our review confirms women are markedly underrepresented in CRT trials, and when a CRT device is implanted, women have a therapeutic response that is equivalent to or better than in men, while there is no difference in adverse events reported by sex.