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Implantable cardiac monitoring might improve outcomes in a broader population with heart failure (HF), according to the GUIDE-HF trial, though the findings were potentially hampered by the COVID-19 pandemic.

The trial tested the CardioMEMS pulmonary artery pressure monitoring device beyond the New York Heart Association (NYHA) Class III indication it gained from the .

The 1,000 patients included in had NYHA Class II to IV heart failure, but the trial also expanded to include the entire left ventricular ejection fraction spectrum and those considered high risk based on elevated natriuretic peptides, not just patients with HF hospitalization in the prior 12 months.

The trial missed its primary endpoint, with no significant difference in a composite of all-cause mortality, HF hospitalization, and urgent HF hospital visits at 12 months between patients with and without CardioMEMS device hemodynamic data to guide management (0.563 vs 0.640 events per patient-year, HR 0.88, 95% CI 0.74-1.05).

However, enrollment closed for the trial shortly before the pandemic began, and follow-up ended during one of the worst surges in January 2021.

A significant interaction emerged between the COVID era and the impact of monitoring, reported JoAnn Lindenfeld, MD, of Vanderbilt Heart and Vascular Institute in Nashville, during the virtual European Society of Cardiology congress. Results of the study were also simultaneously published online in .

The trajectory of outcomes didn't change for the monitored patients, while the control group had a 21% dip in endpoint events during the pandemic.

In a prespecified analysis looking only at the 74% of endpoints occurring before the U.S. national emergency declaration on March 13, 2020, hemodynamic monitoring did reduce deaths and hospitalizations or urgent visits for HF by a relative 19% (P=0.049).

That difference was driven by HF hospitalizations (HR 0.72, 95% CI 0.57-0.92).

HF hospitalizations did drop at many centers in the early part of the pandemic, Lindenfeld noted, pointing to the 65% reduction at her center as an example. However, closer analysis showed that rather than a care-avoidance effect, HF patients simply seemed to do better on standard management during the pandemic, she said.

Factors could be "improved patient compliance with medical and dietary regimens, reduced respiratory infections, altered healthcare provider behavior, changes in disease progression due to COVID-19, or other as yet unknown effects of a major pandemic," the researchers wrote.

A similar scenario played out in the , in which intravenous iron had a neutral effect on HF hospitalizations and cardiovascular death overall, but a benefit when evaluated through a COVID-19 sensitivity analysis. Other HF trials are likely to have the same problem, Lindenfeld's group speculated.

Overall, the trial results appeared highly consistent with those from CHAMPION, Lindenfeld said. "Now with GUIDE-HF including Class II and patients who have not had a heart failure hospitalization but just have elevated natriuretic peptides ... we can get to patients much earlier."

An called the findings "encouraging but inconclusive."

The study population wasn't ideal, argued John Cleland, MD, of the University of Glasgow in Scotland, and Pierpaolo Pellicori, MD, of Imperial College London, "since many had baseline pressures in the target range with little possibility of short-term gain, follow-up was too short, and interventions did not substantially change pulmonary artery pressure."

ESC study discussant Rory Collins, MD, of the University of Oxford in England, cautioned that while the FDA signed off on a P=0.15 threshold for significance in the interaction term that would prompt a COVID impact analysis, it's not a good test for heterogeneity, nor the one used for other subgroups in the trial. The analysis was done after finding P=0.11 for interaction.

Another challenge to interpretation was the greater number of study withdrawals in the control group (44 vs 25), suggesting a lack of blinding that could have affected likelihood of hospitalization, he pointed out.

"I accept the point that potentially the intervention is effective, but one has to put the greatest emphasis on the overall result," Collins argued. "A promising direction of effect, but I don't think conclusive on its own."

Hot Line trial session panelist Stuart Spencer, PhD, the Lancet editor who worked on the paper, agreed that this "effectively positive" trial was a "good start," but warrants another confirmatory trial.

A large, simple, open-label trial looking at a system of care rather than a single technology might be the answer, Cleland and Pellicori wrote.

Cost could be an issue of spreading the monitoring device into a broader population, noted ESC press conference panelist François Schiele, MD, PhD, of University Hospital Jean Minjoz in Besançon, France.

However, CHAMPION showed cost-effectiveness of the device in Class III heart failure, Lindenfeld said. A cost-effectiveness analysis is planned for GUIDE-HF as well.

The trial results appeared consistent across reduced and preserved ejection fraction groups, men and women, and by age and etiology of the cardiomyopathy. Effects were largely consistent across NYHA class, with the exception of a trend in the wrong direction for Class IV patients. Lindenfeld cautioned, though, that there were only 54 patients in that advanced HF group.

Secondary endpoints showed no advantage to CardioMEMS monitoring for total HF events, health-related quality of life, or functional capacity as assessed by 6-minute walk test distance.

Both the usual care and monitoring groups had the congestion-monitoring device implanted and uploaded its data daily, but only the monitoring group had that data reported to treating physicians. Physicians were recommended to titrate diuretics based on monitoring that suggested evidence of excess intravascular volume and to titrate vasodilators if the device indicated elevated vascular resistance.