Regenerative Therapy Makes Headway in HF … in the Right Patients – MedPage Today

Cell-patch therapy was safe and feasible for nonischemic dilated cardiomyopathy (NIDCM), and Japanese researchers reported being a step closer to identifying which patients are most likely to benefit.

Autologous skeletal cell-patch implantation was performed on 24 NIDCM patients, of whom 13 enjoyed freedom from subsequent heart failure events over follow-up averaging almost 2 years, according to Yoshiki Sawa, MD, PhD, of Osaka University Graduate School of Medicine, and colleagues.

These responders to cell patching also showed postoperative improvements in New York Heart Association symptoms and 6-minute walk test results, along with a nonsignificant trend toward greater cardiac performance measured by the left ventricular (LV) stroke work index.

Moreover, the actuarial survival rate of these patients was 90.9% at 5 years, which was superior to the estimate of 70.9% using the Seattle Heart Failure Model, Sawa's group reported in the Journal of the American Heart Association.

Accordingly, "autologous skeletal stem cell-patch implantation might promise functional recovery and good clinical outcome in selected patients with NIDCM, in addition to safety and feasibility," the investigators concluded.

The Terumo autologous skeletal myoblast sheets used in the study have been conditionally approved in Japan alone.

That LV ejection fraction and pulmonary capillary wedge pressure (PCWP) neither improved nor deteriorated among treatment responders suggested that the stem cell therapy enhanced diastolic performance rather than systolic performance, the authors noted.

"We speculate that this improvement in diastolic performance, especially in regard to filling function and stiffness or reduced PVR [pulmonary vascular resistance], was related to an antifibrotic or angiogenic mechanism enhanced by cell-patch treatment via a cytokine paracrine effect coinciding with preclinical treatment," the team wrote.

In contrast, the 11 remaining participants in the study -- all experiencing continued progression of heart failure -- were deemed nonresponders to cell-patch implantation.

Regenerative medicine has been tested in various iterations as a heart failure therapy to mixed results.

According to the present study, whether a NIDCM patient responds to therapy could be strongly predicted by a model incorporating Btype natriuretic peptides, PCWP, and expression of histone H3K4me3 (area under the curve 0.96, P<0.001), Sawa and colleagues found.

In an accompanying editorial, Joshua Hare, MD, of the University of Miami Miller School of Medicine, and colleagues cited their own previous work identifying DCM patients without pathologic genetic variants as being more likely to respond to cell delivery. This concept is being tested in DCMII, a larger, ongoing trial.

NIDCM is a progressive disease that is the underlying etiology of 36% of heart failure with reduced ejection fraction cases, the editorialists noted. The condition has no known cure and is further characterized by a diverse pathogenesis and distinct subtypes sharing a common phenotype.

The 24 NIDCM patients in the study all had LV ejection fraction <35% on optimal medical therapy when they were enrolled from 2010 to 2017. They were required to be in stable condition with no change in medication or additional intervention during the course of the study.

The cause of NIDCM was idiopathic dilated cardiomyopathy in 21 patients, dilated phase of hypertrophic cardiomyopathy in two, and postmyocarditis in one.

For the cell-patching procedure, muscle specimens were harvested from each person's thigh, cultured, and implanted over the left ventricle through a left minithoracotomy.

Sawa's team reported no procedure-related complications or lethal arrhythmias. All patients required postoperative IV catecholamine support, and were discharged to home at a mean 47.3 days following the procedure.

Limitations of the study, the researchers said, included the lack of a control group and follow-up cardiac biopsy to assess the effect of cell patching on fibrosis.

"At a minimum these findings can be viewed as hypothesis generating and could assist in patient selection for future trials," Hare and co-authors said.

A separate team had previously found promising results for autologous bone marrow stem cell injections into the heart in ischemic dilated cardiomyopathy.

Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The research was supported by Japanese grants, with additional funding from Terumo.

Sawa reported research grants to Osaka University and patent fees from Terumo; a co-author reported honoraria from Terumo.

The editorialists disclosed funding from the U.S. Department of Defense; Hare reported grants from the NIH and the Marcus and the Soffer Family Foundations.

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Regenerative Therapy Makes Headway in HF ... in the Right Patients - MedPage Today