The CardioMEMS HF System (Abbott), a wireless pulmonary artery (PA) sensor, was demonstrated to safely reduce heart failure (HF) hospitalizations in the randomized, single-blinded study of 550 patients, CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association Class III Heart Failure Patients (CHAMPION) trial,1 supporting its approval by the US Food and Drug Administration (FDA) and endorsement in the European HF guidelines.2 Since commercial release,3,4 the device has been implanted in older patients with greater burden of medical comorbidities and higher baseline PA pressures compared with those enrolled in the CHAMPION study.1 Although consistent reductions in PA pressures3 and HF hospitalizations4 have been observed with initial real-world use, limited safety data are available after market introduction. We leveraged data from the publicly available Manufacturer and User Facility Device Experience (MAUDE) database to identify CardioMEMS HF System–related adverse events within the first 3 years of FDA approval.
The MAUDE passive surveillance system5 collects mandatory and voluntary reports of device-related malfunctions, injuries, or deaths received by the FDA. We queried all available adverse event reports from May 28, 2014 (date of FDA premarket approval), to May 28, 2017, using search limits by product class (“system, hemodynamic, implant”), model number (“CM1000,” “CM1010,” “CM2000,” and “CM3000”), brand name (“CardioMEMS” and “HF Sensor Delivery System”), and product code (“MOM,” a unique FDA designation linked to the CardioMEMS HF System device). Analyses began in June 2017. An estimate of total device implants in the United States was obtained by sequential review of investor reports and press releases,6 corroborated by a direct source from Abbott. Although this surveillance system cannot be used to establish definitive event rates, we provide estimates of device-, system-, or procedure-related adverse event rates. All MAUDE reports were publicly available with deidentified patient information. Thus, this study was exempt from institutional review board approval.
During the first 3 years after FDA approval, there were more than 5500 total CardioMEMS HF System implants in the United States. Of these approximately 5500 implants, we identified 155 reports (2.8%) describing 177 unique adverse events during this reporting interval. The median time between the date of event and the date the FDA received a report was 42 days (interquartile range, 13-196 days), with 36 reports completed within 1 week of the event. Of 155 reports, 147 were mandatorily reported by the manufacturer/user facility (94.8%). Overall adverse events accrued gradually during this time, but reports of PA injury/hemoptysis and deaths were clustered early after device introduction and appeared to stabilize over time (Figure). Of approximately 5500 implants, there were 28 reports of PA injury/hemoptysis (0.5%), which included 14 intensive care unit stays, 7 intubations, and 6 deaths. Eighteen technical challenges with implantation were reported, of which 14 were aborted. Sensor failure, malfunction, or migration occurred in 46 cases, of which 35 required recalibrations, 13 reimplantations, and 11 hospitalizations (for reintervention, HF, or over-diuresis). Five sensors could not be used despite recalibration. Access site–related bleeding/infection (n = 15) and pulmonary embolism/device thrombosis (n = 5) were also reported. There were 22 total deaths (approximately 0.4%) (6 after PA injury/hemoptysis, 4 HF-related, and 12 unknown or likely unrelated) included in MAUDE reports (Table). Limited details regarding patient histories were available, and no autopsies were reported.
In the CHAMPION trial,1 there were 15 adjudicated serious adverse events (2.6%) with 575 implant attempts, including 1 case of PA injury and 2 deaths. These postmarketing surveillance data provide an early look at the real-world safety profile of this device in less selected, higher-risk patients, demonstrating comparable estimated overall adverse event rates with the CHAMPION trial. However, these data bring greater attention to infrequent but potentially consequential risks of PA injury and need for reintervention or device recalibration. Similar to other interventional therapies, a learning curve may exist for the most serious observed complications (PA injury/hemoptysis and death). Careful candidate selection (patients well represented in the CHAMPION trial and included in the FDA label), greater operator training, and technological refinement (focused on minimizing risk of downstream sensor failure or need for recalibration) may improve device safety and durability.
The FDA relies on several mechanisms to assess the safety of regulated devices after approval and market release. The Manufacturer and User Facility Device Experience database, being only 1 such surveillance system, is subject to certain limitations (incomplete patient profiling; underreporting, delayed reporting, or selective reporting; and lack of quality control or event adjudication). Given these shortcomings, these safety signals will need to be contextualized alongside other, parallel postmarketing surveillance efforts (ClinicalTrials.gov Identifier: NCT02279888) and potentially tracked in a dedicated CardioMEMS HF System registry.
Early detection of safety signals and general oversight of medical devices are challenging. The FDA receives more than 1 million device-related reports annually but has limited resources, clinical reviewers, and knowledge of total device use (the “denominator”) to understand their clinical significance. Future partnerships between regulators, industry sponsors, and academia may help better triage available resources toward improving patient selection, operator experience, or device technology to optimize device use in clinical practice.
Corresponding Author: Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, 75 Francis St, Boston, MA 02115 (email@example.com).
Accepted for Publication: August 29, 2017.
Published Online: September 18, 2017. doi:10.1001/jamacardio.2017.3791
Author Contributions: Dr Vaduganathan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Vaduganathan, Butler, Mehra.
Acquisition, analysis, or interpretation of data: Vaduganathan, DeFilippis, Fonarow, Mehra.
Drafting of the manuscript: Vaduganathan, DeFilippis, Butler, Mehra.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Vaduganathan.
Administrative, technical, or material support: Vaduganathan.
Study supervision: Butler, Mehra.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Vaduganathan is supported by postdoctoral training grant T32HL007604 from the National Heart, Lung, and Blood Institute. Dr DeFilippis reports no conflicts of interest. Dr Fonarow reports significant consulting for Novartis and modest consulting for Amgen, Janssen Pharmaceuticals Inc, Medtronic, and St Jude Medical (now Abbott, the company that currently markets the CardioMEMS HF System). Dr Butler has received research support from the National Institutes of Health and the European Union and has been a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen Pharmaceuticals Inc, Novartis, Relypsa Inc, ZS Pharma Inc, Medtronic, Merck & Co, and CVRx. Dr Mehra is a consultant for St Jude Medical (now Abbott, the company that currently markets the CardioMEMS HF System), Medtronic, Janssen Pharmaceuticals Inc, Stealth Biotherapeutics, Teva (now Mesoblast), NupulseCV Inc, and Portola Pharmaceuticals.
Disclaimer: Dr Fonarow is a section editor of JAMA Cardiology, but he was not involved in any of the decisions regarding review of the manuscript or its acceptance.
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