Endocarditis Persists Five Years After Transcatheter Deployment of Melody Valve Prosthesis in Pulmonary Position

The results of a study conducted by Doff B. McElhinney and his colleagues published in JACC showed that endocarditis is an important adverse outcome following Transcatheter Pulmonary Valve Replacement (TVPR) in children and adults with postoperative congenital heart disease involving the right ventricular outflow tract (RVOT). Ongoing efforts to understand, prevent, and optimize management of this complication are paramount in making the best use of TPV therapy.

Percutaneous placement of a bioprosthetic pulmonic valve in 2000 ushered in the era of transcatheter valve placement. In congenital heart disease patients, especially adolescents and adults, a nonsurgical approach to managing severe pulmonic insufficiency received ready acceptance. Reduced acute morbidity and longer intervals between sternotomies were considered key advantages. Over time, endocarditis emerged as one of the most concerning adverse outcomes in patients with congenital anomalies involving the right ventricular outflow tract (RVOT) and prosthetic valves. Hence, the investigators aimed to evaluate rates and potential risk factors for endocarditis after transcatheter pulmonary valve replacement in the prospective Melody valve trials. All patients in whom a transcatheter pulmonary valve (TPV) was implanted in the RVOT as part of 3 prospective multicenter studies comprised the analytic cohort. The diagnosis of endocarditis and involvement of the TPV were determined by the implanting investigator.

The study was designed such that a total of 309 patients underwent transcatheter pulmonary valve replacement (TPVR) and were discharged with a valve in place. The median follow-up duration was 5.1 years, and total observation until study exit was 1,660.3 patient-years. Endocarditis was diagnosed in 46 patients (median 3.1 years after TPVR), and a total of 35 patients were reported to have TPV-related endocarditis (34 at the initial diagnosis, 1 with a second episode). Moreover, the annualized incidence rate of endocarditis was 3.1% per patient-year and of TPV-related endocarditis was 2.4% per patient-year. At 5 years post-TPVR, freedom from a diagnosis of endocarditis was 89% and freedom from TPV-related endocarditis was 92%. By multivariable analysis, age ≤ 12 years at implant (hazard ratio: 2.3; 95% confidence interval:1.2 to 4.4; p ¼ 0.011) and immediate post-implant peak gradient $15 mm Hg (2.7; 95% confidence interval: 1.4 to 4.9; p ¼ 0.002) were associated with development of endocarditis and with development of TPV-related endocarditis (age #12 years: 2.8; 95% confidence interval: 1.3 to 5.7; p ¼ 0.006; gradient $15 mm Hg: 2.6; 95% confidence interval:1.3 to 5.2; p ¼ 0.008).

The investigators concluded that endocarditis was an important adverse outcome after TVPR and in children and adults with postoperative CHD involving the RVOT. They cautioned that clinicians should maintain a high level of concern about endocarditis with Staphylococcus aureus, which was most often associated with severe clinical presentation and mortality. According to them, a clinical classification system proposed in this report could help standardize approaches to this complication of TPVR and facilitate efforts to analyze and pool data across studies. It would be important to determine risk factors not only for endocarditis generally but in particular for endocarditis manifesting with severe RVOT obstruction and clinical instability. Ultimately, ongoing efforts to understand, prevent, and optimize management of this complication would be paramount in making the best use of TPV therapy. Given the prevalence of mitigating and predisposing conditions and the high risk of endocarditis in this population overall, efforts to educate patients and caregivers about risk and about best practices for risk reduction would be essential to reduce endocarditis rates after TPVR. Future research could be directed toward finding better systems for assessing the severity and clinical outcomes of endocarditis for use in patients with repaired right-sided congenital heart defects, including those with prosthetic pulmonary valves or conduits.

Speaking of the trial in an accompanying editorial titled ‘Transcatheter Pulmonic Valve Replacement: Progress and Pitfalls,’ Dr. William R. Davidson remarked, “The authors have increased our understanding of IE of the valve. A serious hemodynamic syndrome has been better described, but new questions have been raised. Rapid application of new techniques to treat congenital heart disease is often justified by urgent need and the lack of sufficient patients for large trials. This approach has not consistently benefited patients. Years may be necessary to place a therapy in its proper place in the therapeutic armamentarium.” He added, “The partnership among clinicians, investigators, and industry demonstrated here is crucial to progress in rapidly evolving but smaller clinical fields such as congenital heart disease. Partnerships with registries designed for quality improvement and research, such as the American College of Cardiology National Cardiovascular Data Registry-IMPACT and the Transcatheter Valve Therapy registries, would enhance the collection of high-quality data.” Addressing the question about the next step, he said, “Mechanisms to cross-link these registries, with tools and funding to centrally adjudicate imaging findings and case definitions, are next and necessary steps for the field of congenital and structural interventions.”