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While management of dilated cardiomyopathy (DCM) patients whose ejection fraction recovers to above 40% has been becoming more clear, some aspects of optimal medication strategy remain muddy.

Release of the 2022 American College of Cardiology/American Heart Association guidelines on heart failure brought a new category -- heart failure with improved ejection fraction, or HFimpEF -- to mark patients whose left ventricular EF (LVEF) had been below 40% but subsequently rose above that threshold.

DCM is expected to account for a large proportion of this patient subgroup, given the prevalence of reversible causes among its etiologies, noted Claudia Gidea, MD, medical director of the Advanced Heart Failure Program at Newark Beth Israel Medical Center in New Jersey.

"With dilated cardiomyopathy, depending on its etiology, it's easier to recover than restrictive cardiomyopathy," for instance, she said.

Among DCM cases, only perhaps 10-20% of patients overall will recover, Gidea suggested.

But some one-third of peripartum cardiomyopathy patients can be expected to improve with treatment, and the numbers are similar for viral cardiomyopathy and sleep apnea-related cardiomyopathy as well, said Sabahat Bokhari, MD, director of the Cardiac Amyloidosis and Cardiomyopathy Center at Robert Wood Johnson University Hospital in New Brunswick, New Jersey, in an interview monitored by his institutional media relations.

And alcohol-related cardiomyopathy may go away entirely as long as patients remain abstinent, Gidea added.

The new HFimpEF subgroup contains what had provisionally been called HF with recovered EF. However, the guidelines argued that it is actually remission -- not recovery, as rebounding to an LVEF above 40% or even above 50% "does not mean full myocardial recovery or normalization of LV function," despite better outcomes than continued low LVEF.

"In most patients, cardiac structural abnormalities, such as LV chamber dilatation and ventricular systolic and diastolic dysfunction, may persist," the guidelines point out. "Furthermore, changes in LVEF might not be unidirectional; a patient may have improvement followed by a decrease in EF or vice versa depending on the underlying cause, duration of disease, adherence to the GDMT [guideline-directed medical therapy], or re-exposure to cardiotoxicity."

For this reason, the guidelines made a class I recommendation that HFimpEF patients should stay on their guideline-directed medication therapy to prevent relapse, even if they become asymptomatic.

"In the past when we used to stop the medication or reduce the doses in these patients, there was a higher rate of relapse in those patients," he noted.

What proved the point was the data released in 2019. In it, patients with previous DCM whose LVEF had improved from less than 40% to at least 50% along with normalization of LV end-diastolic volume and N-terminal pro-B-type natriuretic peptides (NT-proBNP) concentration was less than 250 ng/L were randomized to either phased withdrawal of medication or continued treatment.

Over the first 6 months, 44% of patients who stopped medications had their LVEF drop by more than 10% and to below 50% or had other clinical evidence of HF pointing to relapse, whereas none had relapse in the group that continued medication. When patients who were initially assigned to stay on their medication tried withdrawing it after the 6 month point, 36% of them had relapse as well.

Secondary analyses showed worsening quality of life along with nonsignificant increases in NT-proBNP and LV volumes with withdrawal of HF medications.

In an from China, 58% of HFimpEF patients with DCM who chose to stop taking spironolactone relapsed within 12 months compared with 13% of those who stayed on the drug, again with symptoms and cardiac structure parameters favoring continuation.

The difference was less dramatic but still significant for beta-blocker use versus nonuse in a with recovered DCM, with 19.6% versus 24.0% relapsing at 2 years.

However, the only randomized trial -- TRED-HF -- was a pilot trial of 51 patients. And none of the studies addressed whether reducing doses without stopping medication might have been as good.

A common strategy, though, is once the EF has improved, "bring the dosage down a little bit, which patients can easily tolerate and keep them at least on a low-dose beta-blocker and ACE inhibitor," Bokhari noted. "So they can take off the other medications, which are MRA [mineralocorticoid receptor antagonist] and also switch them to ACE inhibitors instead of ARNI [angiotensin receptor/neprilysin inhibitor]."

"There is not that much data right now for continuing SGLT2 inhibitors, because those are relatively new," he added.

Nor is it "absolutely clear" whether patients need lifelong continuation of these therapies, given the lack of data, Bokhari noted.

Despite the lack of consensus, Gidea said, "As long as they are recovered on their current medical regimen, I continue until end of their life the same regimen, even if they have improvement in their ejection fraction."

Helping patients to stick to their management plan even after many measures of their condition normalize can take some effort, she acknowledged.

"Positive reinforcement, education, and collaborative discussions are required in order to assure patient compliance and therapy success," she said. "The patient has to be an integral part of the therapy plan, including not only medicines but lifestyle changes [and] physical, social, and behavioral activities."

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