First-in-Human Report Highlights Challenges of Harmony Valve Endocarditis and Surgical Removal

A newly published case report in JACC: Case Reports details the first known surgical explantation of a Harmony self-expanding transcatheter pulmonary valve because of endocarditis, highlighting significant technical challenges associated with valve removal and raising questions about the long-term management of this novel device.

The Harmony valve (Medtronic) is the first FDA-approved self-expanding transcatheter pulmonary valve developed for treatment of severe pulmonary regurgitation (PR) in patients with a native or surgically repaired right ventricular outflow tract (RVOT). Its design enables transcatheter intervention in a broader range of anatomies, particularly benefitting adult patients who have undergone tetralogy of Fallot (TOF) repair. However, until now, data on the risk of endocarditis with this valve have been limited, and no accounts of surgical explantation after infection have been published.

This case report describes a 26-year-old man with TOF repaired in infancy via a transannular patch, who underwent transcatheter pulmonary valve replacement (TPVR) at age 24 with a 25-mm Harmony valve for severe symptomatic PR. Post-procedural imaging confirmed a well-functioning valve with trivial regurgitation and a mild peak gradient of 22 mm Hg.

Two years later, the patient presented with fever, shortness of breath, and malaise. He was found to have leukocytosis, acute kidney injury, and blood cultures positive for Staphylococcus aureus. Despite inpatient treatment and outpatient IV administration of cefazolin for a skin infection related to eczema, the patient experienced a recurrence of symptoms. A transesophageal echocardiogram revealed bulky vegetations on the valve with moderate stenosis (peak gradient, 50 mm Hg) and mild regurgitation. CT imaging corroborated these findings.

The patient was admitted to the hospital for antibiotic therapy. Despite clinical improvement, recurrent infection and imaging findings prompted surgical valve excision. Intraoperative findings revealed substantial challenges. The self-expanding Harmony valve was deeply embedded and endothelialized within the RVOT myocardium, with extensive skirt extension into the main pulmonary artery (PA). The PA and surrounding tissues were notably indurated and edematous.

“Surgical dissection of the valve was more complex than removal of a standard surgical valve,” said David Gregg, MD, one of the report authors. “The stent skirt extended into the right ventricular myocardium and pulmonary artery.”

Although freeing the valve from the RVOT was particularly difficult, detaching it from the PA and valve annulus was less complex. Cardiopulmonary bypass time was 122 minutes. Inspection of the removed valve confirmed small vegetations on the distal end, thickened dysfunctional leaflets, and no large obstructing mass. The surgical team implanted a 26-mm aortic homograft conduit from the right ventricle to the PA.

This report is the first to provide visual and procedural details of Harmony valve explantation due to endocarditis. The authors note that this valve’s extensive skirt and self-expanding nitinol frame, which allow for broader anatomical compatibility, may also contribute to complex surgical removal. The Harmony valve’s ability to embed in myocardial tissue could complicate future interventions, particularly in young patients who may require multiple valve replacements over a lifetime.

“We found the case illustrative and important, as [it] highlights one of the tradeoffs of less invasive transcatheter therapy with what appears to be higher rates of endocarditis than surgical valves, and in the case of this self-expanding valve, a large complex stent that may be more challenging to surgically extract,” said Dr. Gregg.

A recent analysis of 243 patients who have undergone TPVR identified six cases of endocarditis, with two requiring valve explantation—neither of which had published clinical details before this report. The current lack of data may reflect the relatively recent adoption of this technology rather than a lower infection risk.

Although the authors remain supportive of transcatheter approaches, they caution that such therapies must be weighed carefully during lifelong valve management planning. “Our group remains incredibly enthusiastic for the Harmony valve and other transcatheter valves in treatment of pulmonary valve disease,” Dr. Gregg said. “The advantages of less invasive valve replacement are enormous, and we certainly see the role of transcatheter therapies continuing to grow. We just want to highlight that transcatheter therapy is not a ‘free lunch’—there are trade-offs including endocarditis and reoperation challenges that are particularly important to remember in younger patients who will likely need numerous procedures over a lifetime.”

The case underscores the importance of balancing the benefits of less invasive valve therapies with potential long-term complications. Although transcatheter valve systems such as the Harmony valve reduce the need for open surgery, they may introduce unique risks, including challenging reoperations and uncertain infection profiles. Rates of endocarditis in earlier-generation TPVR systems have reached up to 16.9% at 8 years.

As self-expanding valves become more widely used, further documentation of endocarditis risk and surgical challenges will be critical. The authors emphasize the need for continued evaluation of long-term outcomes, surgical implications, and optimal timing of valve replacement in patients with congenital heart disease, particularly those with TOF.

This case report offers early insights into real-world management of Harmony valve complications and highlights the necessity of informed decision-making when selecting valve type and timing for younger patients with evolving needs.

Gregg D, et al. JACC Case Rep. 2025 doi:10.1016/j.jaccas.2025.103516