Doff B. McElhinney

The Melody® valve and Ensemble® delivery system for transcatheter pulmonary valve replacement

The Melody® transcatheter pulmonary valve (TPV) is a percutaneous valve system designed for the treatment of obstruction and/or regurgitation of prosthetic conduits placed between the right ventricle and pulmonary arteries in patients with congenital heart disease. In 2000, Melody TPV became the first transcatheter valve implanted in a human; in 2006 it became the first transcatheter valve commercially available anywhere in the world; and in 2010 it was launched as the first commercially available transcatheter valve in the United States. In this review, we present the clinical background against which the Melody valve was developed and implemented, introduce the rationale for and challenges of transcatheter valve technology for this population, outline the history and technical details of its development and use, and summarize currently available data concerning the performance of the device.

Comparison of Reported Outcomes With Percutaneous Versus Surgical Closure of Ruptured Sinus of Valsalva Aneurysm

Sinus of Valsalva aneurysm is a rare cardiac malformation that stems from incomplete fusion of the aortic media and the aortic valve annulus, a weakness that may result in rupture of the sinus, large left-to-right shunt, and severe congestive heart failure. Historically, this lesion has been repaired surgically, but percutaneous closure (PC) has emerged as a therapeutic intervention over the last 20 years. We review and contrast 34 studies detailing the PC approach with 16 studies on surgical closure (SC), together comprising a total of 877 patients who were treated for ruptured sinus of Valsalva aneurysm from 1956 to 2014. Both groups had similar sites of rupture, age distribution, and clinical symptoms at presentation. Selection bias ultimately prohibits a direct comparison between the 2 groups as patients who underwent SC often had worse aortic regurgitation and more complex associated lesions, including endocarditis, bicuspid aortic valve, tunnel-type fistulous connections, larger defect size, and multiple site of rupture. In conclusion, although SC is indicated and reserved for these more complicated patients, our review of previously published reports reveals that PC in patients who are too ill to undergo bypass, with mild or no aortic regurgitation and simple associated defects (muscular ventricular septal defects, secundum atrial septal defect, small patent ductus arteriosus), can be safe, effective, and practical.

Computational simulations of flow dynamics and blood damage through a bileaflet mechanical heart valve scaled to pediatric size and flow.

Despite pressing needs, there are currently no FDA approved prosthetic valves available for use in the pediatric population. This study is performed for predictive assessment of blood damage in bileaflet mechanical heart valves (BMHVs) with pediatric sizing and flow conditions. A model of an adult-sized 23 mm St. Jude Medical (SJM) Regent(™) valve is selected for use in simulations, which is scaled in size for a 5-year old child and 6-month old infant. A previously validated lattice-Boltzmann method (LBM) is used to simulate pulsatile flow with thousands of suspended platelets for cases of adult, child, and infant BMHV flows. Adult BMHV flows demonstrate more disorganized small-scale flow features, but pediatric flows are associated with higher fluid shear stresses. Platelet damage in the pediatric cases is higher than in adult flow, highlighting thrombus complication dangers of pediatric BMHV flows. This does not necessarily suggest clinically important differences in thromboembolic potential. Highly damaged platelets in pediatric flows are primarily found far downstream of the valve, as there is less flow recirculation in pediatric flows. In addition, damage levels are well below expected thresholds for platelet activation. The extent of differences here documented between the pediatric and adult cases is of concern, demanding particular attention when pediatric valves are designed and manufactured. However, the differences between the pediatric and adult cases are not such that development of pediatric sized valves is untenable. This study may push for eventual approval of prosthetic valves resized for the pediatric population. Further studies will be necessary to determine the validity and potential thrombotic and clinical implications of these findings.

Will There Ever Be a Food and Drug Administration–Approved Device for Transcatheter Paravalvular Leak Closure?

Paravalvular leaks (PVLs) have been a recognized problem after surgical valve replacement since prosthetic valves were first implanted for aortic and mitral valve disease 5 decades ago.1 Although the reported incidence varies considerably, it is generally estimated that a PVL of some magnitude is present in ≈7% to 17% of mitral and 2% to 10% of aortic valve replacement prostheses.2–5 Most PVLs are small and inconsequential, but anywhere from 1% to 5% of aortic or mitral valve replacement procedures are complicated by a clinically relevant PVL.2–5 Although the use of transcatheter devices to close prosthetic PVLs was described >20 years ago,6 this procedure remained relatively rare until recently, but with the availability of nitinol mesh devices designed for occlusion of various other communications, transcatheter PVL closure has become a regular, although still somewhat uncommon, procedure for many structural interventional cardiologists.4,5,7–12 Moreover, as transcatheter aortic valve replacement has become increasingly widespread, and paravalvar regurgitation has been recognized as one of its most frequent and significant complications,13 an entirely new domain has opened up, namely, management of PVLs after transcatheter aortic valve replacement.nnLiterature on PVL device closure comprises a handful a modest-sized, single-center series and many more single or small case reports.4,5,7,14–20 Based on these series, device closure is technically unsuccessful in 5% to 35% of cases, for various reasons, including inability to cross the defect with a wire or delivery catheter, dislodgement/embolization of the device, incomplete closure of the defect, or interference by the device with the prosthetic valve. Even if the device is delivered, remains in place, and reduces flow, the treatment may be clinically inadequate, sometimes because of persistent or new hemolysis, and …

A New START for Sildenafil in Pediatric Pulmonary Hypertension: Reframing the Dose-Survival Relationship in the STARTS-2 Trial

Pharmacotherapy for pulmonary arterial hypertension (PAH) has evolved dramatically over the past decade. One of the agents at the vanguard of this evolution was sildenafil, which was reported in 2005 to improve exercise capacity, functional status, and hemodynamics in a large randomized controlled trial (RCT) of adults with PAH (SUPER-1) 1 , and has since become a therapeutic mainstay 2 . Based in part on the promising early findings of SUPER-1, sildenafil was studied in treatment-naive children and adolescents as part of the first ever RCT for pediatric PAH, STARTS-1, which randomized patients to placebo or 1 of 3 dose-ranges of sildenafil 3 . After the 16-week evaluation, patients were allowed to remain on therapy in the extension trial, STARTS-2, which continued sildenafil in treated patients and randomized those in the placebo arm to one of the sildenafil doses. STARTS-1 enrolled 234 patients over 4.5 years at 32 centers, the vast majority of whom continued in STARTS-2.

Pulmonary Valve Replacement in Tetralogy of Fallot

A 32-year-old woman with a history of tetralogy of Fallot (TOF) was referred for cardiac evaluation. She was diagnosed with TOF as an infant and at 8 months of age underwent complete repair, including ventricular septal defect closure, resection of right ventricular (RV) outflow tract (RVOT) muscle bundles, and pulmonary valvotomy. She was evaluated by a cardiologist at 17 years of age and was subsequently lost to follow-up because she thought she was “cured.” Overall, she feels well and denies cardiac symptoms. She runs 1 to 2 miles daily, although more slowly than her friends. She is considering having children.nnOn physical examination, her vital signs were normal. She had a well-healed midline sternotomy scar. Her lungs were clear to auscultation. The heart rhythm was regular with a normal S1 and a single S2. There was a low-pitched, delayed diastolic murmur in the pulmonary area. Her ECG demonstrated normal sinus rhythm, a right bundle-branch block, and a QRS duration of 170 milliseconds.nnA transthoracic echocardiogram showed a dilated and hypokinetic RV, with severe pulmonary regurgitation (PR) and mild tricuspid regurgitation. There was no RVOT obstruction or residual ventricular septal defect. The left ventricle was normal in size and function, with mild mitral regurgitation. Because RV size and function were not well quantified with echocardiography, cardiac magnetic resonance imaging was performed. The RV end-diastolic and end-systolic volumes were 179 and 109 mL/m2, respectively, and the RV ejection fraction was 39%. A Holter study did not reveal significant ectopy or arrhythmia. A cardiopulmonary exercise test demonstrated a moderately depressed peak o2. Given her severe PR associated with a dilated and hypokinetic RV and moderately reduced exercise tolerance, she was referred for surgical pulmonary valve replacement (PVR).nnThis woman is 1 of ≈1 million adults with congenital heart disease …

First-in-Man: Primacy and the Nexus of Innovation in Interventional Cardiology

I have long been intrigued by the fashion for attributing originality by naming a procedure, complex, or clinical sign after the first person to describe it, and by the perseverance with which such eponyms persist. Blalock-Taussig, Norwood, Glenn, Fontan—marks of honor bestowed by the community in a frontier culture—remain prevalent monikers of operations performed for congenital heart disease, decades after introduction, despite the rationalizing simplifications they represent, and in defiance of the many departures that have transformed their original iterations. That historical field brings to mind a surgeon I encountered many years ago who cataloged his personal, if not eponymous, procedural innovations; notches in a belt, akin to a compendium of patents received or invited lectures given. As I began to explore the literature in that field, aiming to develop a better understanding of how technical progress is chronicled in the medical record, it became clear that, just as the fidelity of certain procedural eponyms may be suspect, the novelty and provenance of purported innovations can be ambiguous, and that, more generally, claims of primacy are inherently fraught. Years later, I came to appreciate the implications of that list, similar to but more acquisitive than the historical stream of eponymous procedures in its insinuation that technical innovations are uniquely forged by a single person, that procedural primacy is the embodiment of innovation in interventional medicine.nnInnovation, however, is much more complex, almost inevitably occurring within and evolving from an array of inputs and influences, both successes and failures, emanating from the individual him- or herself, as well as countless predecessors and contemporaries. This observation should go without saying, but it is worth a reminder in the current era, in which innovation has become uniquely esteemed. Accounting for all the influences contributing to the execution of any new procedure, to acknowledge …

Heterogeneity of Regional Function and Relation to Ventricular Morphology in Patients With Fontan Circulation

The relation between underlying ventricular morphology and regional function in patients with Fontan circulation remains unclear. The aim of this study was to compare regional function and its heterogeneity in patients with tricuspid atresia (TA), biventricular apex-forming morphology (BiV), and controls. Nineteen patients (median age 12 years) with Fontan circulation who presented consecutively were prospectively enrolled and compared with age- and heart rate-matched controls. Most patients were in New York Heart Association class I (63%). Longitudinal systolic strain (S), systolic strain rate (SRsys), and early diastolic strain rate (SRdia) peaks were obtained from 6 ventricular segments, and a coefficient of variation by segment was calculated as a measure of regional heterogeneity. Systolic S, SRsys and SRdia peaks were decreased at the right and left lateral walls in both patient groups compared with controls (p ≤0.001 for all). Patients with TA had higher systolic S and SRsys in the middle of the right lateral wall than those with BiV morphology (p = 0.009 and p = 0.001, respectively). The mean coefficients of variation assessed by S and SRsys were similar in controls and patients with TA but lower in those with BiV than in controls and patients with TA (p <0.001 and p = 0.01, respectively). The mean coefficient of variation assessed by SRdia was greater only in patients with BiV than in controls (p = 0.001). In conclusion, patients with Fontan circulation have more heterogeneous systolic and early diastolic regional function than healthy control subjects, and patients with TA have better systolic regional function in the middle of the right lateral wall and less systolic heterogeneity than patients with BiV morphology.

Transcatheter Pulmonary Valve Replacement: A Current Review

Since first reported in 2000, transcatheter (percutaneous) pulmonary valve (TPV) replacement has become an important tool for the management postoperative right ventricular outflow tract (RVOT) dysfunction in patients with congenital heart disease, either as alternative or adjunct to surgery. Implantation of a pulmonary valve for treatment of RVOT obstruction or pulmonary regurgitation without performing open-heart surgery offers obvious appeal, and short-term results from multiple institutions throughout the world support the effectiveness and safety of this therapy. At present, there are two TPV prostheses available in the U.S.: the Medtronic Melody® valve is available commercially, and the Edwards Sapien® valve is available at limited centers as part of an investigational protocol. Although TPV therapy is likely to have a major impact on the management of postoperative RVOT dysfunction in patients with congenital heart disease or a Ross procedure, the technology is young and there is much that remains to be learned.

Beyond indications: postmarket surveillance and the importance of expanded and off-label use of transcatheter devices in structural and congenital interventions.

In September of this year, the US Food and Drug Administration (FDA) Center for Devices and Radiological Health published a document entitled, “Strengthening Our National System for Medical Device Postmarket Surveillance.”1 In addition to summarizing the current process and mechanisms for monitoring medical devices after commercial approval, the document proposed the following specific actions to improve the efficiency and quality of postmarket surveillance of medical devices in the United States:nn> 1. Establish a unique device identification system and promote its incorporation into electronic health information; n> n> 2. Promote the development of national and international device registries for selected products; n> n> 3. Modernize adverse event reporting and analysis; and, n> n> 4. Develop and use new methods for evidence generation, synthesis, and appraisal. [1, p. 4] nnThe intended focus of this initiative is laudable and much needed, as the current system, discussed in this journal earlier this year,2 is widely believed to be overly time consuming and expensive, and to place the United States at a competitive and technological disadvantage to many other countries. As with many of the investigational mechanisms used to assess new medical technologies, these initiatives are likely to lend themselves most easily to devices that are used widely and in relatively consistent applications. With the introduction and evolution of this forward thinking upgrade of the postmarket medical device surveillance system, let us hope that low-volume, off-label, and other marginal device use remains within its purview so that we can collectively move toward a better understanding and oversight of such device applications, as well as those with broader market applications.nnIt is no secret that the majority of transcatheter interventions for congenital heart disease in the United States are performed with devices that are not …