DALLAS (FRONTLINE MEDICAL NEWS) – Management of outpatients with advanced heart failure using an implanted pulmonary artery pressure monitor continues to show real-world efficacy and safety at least as impressive as in the pivotal trial for the device.

Data from the first waves of patients to receive the CardioMEMS implanted pulmonary artery pressure (PAP) monitor since it got Food and Drug Administration marketing approval in May 2014 also showed steady uptake of this fluid volume management strategy for patients with advanced heart failure, despite Medicare reimbursement issues in some U.S. regions, J. Thomas Heywood, MD , said at the at the annual scientific meeting of the Heart Failure Society of America. He estimated that more than 6,000 U.S. heart failure patients have now had a CardioMEMS PAP monitor implanted.

“PAP monitoring seems to work in the real world,” said Dr. Heywood, a heart failure cardiologist at the Scripps Clinic in La Jolla, Calif. An apparent signal of better patient outcomes during routine use, compared with outcomes in the pivotal CHAMPION trial (Lancet. 2011 Feb 19; 377[9766]:658-66 ), may reflect a real change in how clinicians use the data from implanted PAP monitors, he speculated.

“The clinicians using CardioMEMS now have a lot more experience” than they had during the trial, he said in an interview. “They have more experience using the device, they know what treatments to use to lower PAP more effectively, and they are now convinced that patients will benefit from reducing diastolic PAP.”

Dr. Heywood estimated that tens of thousands more U.S. heart failure patients with New York Heart Association class III disease and a recent history of at least one heart failure hospitalization are eligible to receive an implanted PAP monitor, dwarfing the more than 6,000 patients who received a device so far.

The postapproval study

The newest efficacy data come from the first 300 patients enrolled in the CardioMEMS HF System Post Approval Study , a registry of patients receiving an implanted PAP monitor funded by the device’s manufacturer and scheduled to include a total of 1,200 patients. Dr. Heywood said full enrollment was on track for completion by the end of October 2017.

The first 300 patients enrolled in the postapproval study were older than the CHAMPION cohort; they averaged about 69 years of age, compared with about 62 years in CHAMPION, were more often women (38% vs. 28% in CHAMPION), and were more likely to have heart failure with preserved ejection fraction (41% vs. about 22%).

Follow-up data showed that, during the first 6 months with PAP monitoring, the 300 patients averaged 0.20 hospitalizations for worsening heart failure, with 56 hospitalizations in 43 patients (14%), reported Nirav Y. Raval, MD , a cardiologist at Florida Hospital in Orlando. In contrast, in CHAMPION the average heart failure hospitalization rate during 6 months was 0.44 in control patients and 0.32 in those managed using frequent monitoring of an implanted PAP device.

A similar pattern existed for the 6-month cumulative tally of PAP area under the curve, which showed an average rise of 42 mm Hg/day in the CHAMPION control patients, an average drop of 160 mm Hg/day in the CHAMPION patients managed using their CardioMEMS data, and a drop of 281 mm Hg/day in the 300 postapproval study patients.

“We’re now using the implanted sensor in a broader population of patients, and one wonders whether the effect will be diluted. What we see is at least as good as in the CHAMPION trial. This is just an early snapshot, but it is exciting that we see no erosion of the benefit. It’s a great indication that the correct patients are receiving it,” Dr. Raval said while presenting a poster at the meeting.

Further scrutiny of the same 300 patients showed another feature of the impact of PAP monitoring on patient outcomes: The first 90 days with the PAP monitor in place led to a greater number of tweaks in patient treatment and a steady fall in PAP. During days 91-180, PAP tended to level off, the number of medication adjustments dropped, and heart failure hospitalizations fell even more than in the first 90 days, Joanna M. Joly, MD , reported in a separate poster at the meeting.

During days 0-90, heart failure hospitalizations averaged a 6-month rate of 0.29, but during days 91-180 this dropped to an average 6-month rate of 0.11, said Dr. Joly, a cardiologist at Brigham and Women’s Hospital in Boston. Also during the first 90 days, the 300 patients underwent 1,226 medication changes, most often drug up-titrations with a diuretic or with nitrates. During days 91-180, this fell by nearly half, to 660 medication changes, a rate of 2.2 changes per patient during the second set of 90 days or fewer than 1 medication change per month in each patient, she reported.

The data showed “effective reduction” of PAP during the second half of the study despite fewer medication adjustments. How was that possible? Patients who transmit data on their PAPs undergo “modeling of their behavior” based on the feedback they receive from the device, Dr. Joly suggested. Regular measurement of their PAP and seeing how the number relates to their clinical status helps patients “understand the impact of their nonadherence to diet and their medications.” Another factor could be the growing familiarity clinicians develop over time with PAP fluctuations that individual patients display repeatedly that are usually self-correcting. Also, patients may undergo “hemodynamic remodeling” that results in improved self-correction of minor shifts in fluid volume and vascular tone, she said.

This pattern of a reduced need for interventions after the first 90 days with a PAP implant suggests that many patients managed this way may be able to transition to care largely delivered by local providers, or even play a greater role in their own self-care once their PAP and clinical state stabilizes, Dr. Joly said.

The findings imply that by the end of the first 90 days, “patients accept the device and manage themselves better. It becomes basically a behavioral device” that helps patients better optimize their diet and behavior, Dr. Raval observed.

Safety holds steady

Continued real-world use of PAP monitoring has also resulted in new safety insights. During the first 3 years when the CardioMEMS device was on the U.S. market, May 2014–May 2017, the FDA’s adverse event reporting system for devices, the Manufacturer and User Facility Device Experience ( MAUDE ) received reports on 177 unique adverse events in 155 patients implanted with a PAP monitor, Muthiah Vaduganathan, MD , reported at the meeting. During the same 3-year period, he estimated that at least 5,500 U.S. patients had received a CardioMEMS device, based on data Dr. Vaduganathan obtained from the manufacturer, Abbott. This works out to an adverse event rate of about 2.8%, virtually identical to the rate reported from CHAMPION, noted Dr. Vaduganathan, a cardiologist also at Brigham and Women’s.

The most common adverse event was a sensor failure, malfunction, or migration, which happened in 26% of the patients, followed by pulmonary artery injury or hemoptysis, which occurred in 16%. MAUDE reports for the device included 22 deaths, including six patients who died as a result of pulmonary artery injury or hemoptysis, four patients who died from a heart failure–related cause, and 12 patients with death from an unknown cause or a cause unrelated to their heart failure or CardioMEMS placement.

Analysis of both the 22 deaths as well as the episodes of pulmonary artery injury or hemoptysis showed that the preponderance occurred relatively early after introduction for U.S. use, suggesting that “a learning curve may exist for the most serious complications,” he said. “Improved safety and device durability may result from careful patient selection, increased operator training, and refined technologies.”

Dr. Vaduganathan cautioned that the MAUDE database is limited by its bias toward serious adverse events, selective reporting, and lack of adjudication for the reported events. Concurrently with his report at the meeting, a written version appeared online (JAMA Cardiol. 2017 Sep 18. doi:10.1001/jamacardio.2017.3791 ).

“The adverse event rate was reassuringly low, well below the accepted threshold for device safety. It bodes favorably for the device,” he said in an interview.

“But with a passive surveillance system like MAUDE, adverse events are likely underreported; we see in MAUDE the most severe adverse events. There is certainly a larger spectrum of more minor events that we are not seeing, but I think these numbers accurately reflect serious events.” A full registry of every U.S. patient who receives the device, similar to what’s in place for U.S. patients who undergo transcatheter aortic valve replacement, would provide a more complete picture of the risks, Dr. Vaduganathan suggested.

He also voiced some surprise about the frequency of pulmonary artery injury, which was not as apparent in the 550 total patients enrolled in CHAMPION. Clinicians who place the PAP monitor are required to first take a training program, but the manufacturer has no mandated minimum number of placements an operator must assist on before launching a new CardioMEMS practice, Dr. Vaduganathan said. Many of the pulmonary artery injuries reported to MAUDE resulted from wire perforations that resulted from loss of wire control, he noted.

Clarifying the optimal CardioMEMS recipients

PAP monitoring for patients with advanced heart failure “is a major advance for certain patients who have historically been very challenging to manage,” especially patients with heart failure with preserved ejection fraction, which has few other treatment options. But “it’s often difficult to know when to pull the trigger” and proceed with placing a PAP monitor in an eligible patient, he said. “Greater experience will help us better understand that,” Dr. Vaduganathan predicted.

Dr. Heywood said that, in addition to the standard criteria of NYHA class III symptoms and a recent history of a heart failure hospitalization, the other clinical feature he looks for in a patient who is a possible CardioMEMS recipient is a persistently elevated systolic PAP as measured using echocardiography.

“These are patients with evidence of an ongoing hemodynamic problem despite treatment, and I need more data to do a better job of getting their PAP down.” Although the PAP that patients self-measure once they have the device in place is their diastolic PAP, measuring systolic PAP by echo is usually a good surrogate for finding patients who also have a persistently elevated diastolic PAP, he explained.

Another important selection criterion is to look for the patients who are dying from heart failure rather than with heart failure, Dr. Heywood added.

“If heart failure is the major thing wrong, then we can improve their quality of life” by guiding fluid management with regular PAP measurement, especially patients with preserved left ventricular ejection fraction who have few other treatment options right now, he said.

The CardioMEMS HF System Post Approval Study is sponsored by Abbott, which markets CardioMEMS. Dr Heywood has been a consultant to and/or has received research funding from Abbott as well as Impedimed, Medtronic, Novartis, and Otsuka. Dr. Raval has been a consultant to Abbott. Dr. Joly and Dr. Vaduganathan had no disclosures.

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