CHRI Investigator Feature
While nobody would doubt that infants who need surgery for congenital heart defects are among the most fragile and vulnerable patient populations, outcomes data from these surgeries are sobering. For instance, neonates (<30 days old) undergo about 25% of the surgeries for congenital heart disease in North America, but they incur over half of the surgical mortalities.1 For Dr. James Hammel, Chief of Pediatric Cardiac Surgery, the magnitude of these burdens and the opportunity to reduce them through surgical innovation provide the motivation for a wide-ranging research program. In a recent interview he commented, “What I enjoy about research that I’m participating in now is that outcomes in our field are still not what anybody would like them to be. We are exploring a number of innovative surgical approaches. Surgeons are born problem solvers and innovators.” Those traits, together with a background of rigorous training in translational research (organ transplant immunology), have equipped Dr. Hammel and colleagues to move the field forward through a variety of clinical research studies.
Atrioventricular valve replacement
Defective tricuspid or mitral valves, which cause problems such as stenosis or regurgitation of blood at the passage between atrium and ventricle, are typically addressed by valve replacement. However, one barrier to intervention in small infants is that atrioventricular implants at diameters <15mm are not commercially available. Therefore, Dr. Hammel began collaborating with Dr. Kevin Cole of the UNL Department of Mechanical and Materials Engineering to create and test experimental atrioventricular valves at sizes suitable for small infants. They evaluated prototypes by measuring flow potentials in various sizes of tubes and valves. Ultimately, this quest took a leap forward with the adaptation of a commercial device, the Melody valve (Medtronic), that was originally approved for implantation in the pulmonary conduit of an adult heart. Dr. Hammel and Dr. Jeff Delaney devised modifications to the Melody device and a simple method for implantation by catheter, enabling replacement of mitral or tricuspid valves at “infant-sized” diameters. Valve longevity after implantation proved to be about 2 years. “In an infant, that’s great,” Dr. Hammel noted. “That might get you up to another whole valve size.” CHMC and Boston Children’s Hospital are the only hospitals in the US that use a modified Melody device for this purpose in significant numbers of patients, and CHMC’s simplified implantation method remains unique in the nation.
Full-flow perfusion technique for aortic arch reconstruction
Induced deep hypothermia and circulatory arrest (DHCA) is a very old method to protect brain tissue during heart bypass surgery. While rare in most modern cardiac surgeries, the DHCA method is still standard for aortic arch reconstructions. At almost every other program in the world, babies undergoing arch surgery are cooled to 18-20°C to stop circulation for 30-40 minutes.2 A frequent consequence of this procedure is mild acute kidney injury, which in turn correlates with longer times of ICU stay and mechanical ventilation. In 2014 Dr. Hammel reported the development of an alternative referred to as dual arterial cannulation. This includes a sequence of direct cannulation of the innominate artery, elevation of the heart, and direct cannulation of the descending aorta to ensure continuous blood flow to the entire body.
After CHMC adopted this procedure for newborn infant arch reconstruction surgeries, Dr. Hammel’s team reported improved renal function and shorter operative times, compared with the recent historical cohort of infants who had received the standard procedure in the same clinic. For more robust conclusions, the ideal evaluation would be with a prospective randomized trial. However, this was precluded by ethical concerns over denying the local standard of care to a group of control patients. Dr. Hammel anticipates an answer to this problem through the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database, which compiles data from all 25,000 surgeries registered annually in the US. Propensity score matching techniques make it possible to define a contemporaneous virtual control group from surgeries occurring across the country. By approximating a randomized experiment in this way, Dr. Hammel hopes to produce a statistically robust verdict on the safety of infant aortic arch surgery performed without inducing deep hypothermia.
One potentially impactful multi-center study on which CHMC is just starting to enroll cardiac surgery patients is the STeroids to REduce Systemic Inflammation after Infant Heart Surgery (STRESS) Trial. This Phase 3 placebo-controlled trial seeks to measure the impact of the large methylprednisolone doses that are often given to infant patients in the hours before cardiopulmonary bypass surgery. Data supporting pre-surgery steroids for the infants are very limited, and one study suggested negative effects such as higher incidence of infection. “It’s a cool trial,” remarked Dr. Hammel, “because it also leverages that STS Database participation. It’s what people are calling a ‘pragmatic clinical trial,’ where you only put in the one intervention and you let people do everything else the same, and all of the outcome measures are the data that we’re already reporting to this national database. It’s easy and cheap to have a large number of patients in this trial because we’re not collecting very much data specifically for the trial.” Ultimately, results could pave the way to simpler and safer surgery protocols.
3D Printing and Pediatric Heart Surgery
Three-dimensional (3D) printing technology has already influenced cardiac surgery practices3, including for CHRC’s patients. MRI, CT, or echocardiography source images from a patient are mapped as a computed model in 3D space, and then manifested as a physical model built of thermoplastic or resin materials. Patient-specific heart models make the anatomy of a complicated heart tangible for the surgeon before the operation. In our interview, Dr. Hammel picked up one of the 3D-printed heart models on his desk and explained, “The relationship between the inlets, the pulmonary venous inlet and the systemic venous inlet, and the outlets, is complicated. This outlet looks on the outside of the heart like it’s to the patient’s left and that the pulmonary is on the patient’s right. But this model makes it easier to conceive that actually this aortic outlet is coming more from the right side of the heart and the pulmonary outlet is coming from the left side – but it doesn’t look that way on the outside. That kind of information can be helpful in terms of planning, or really even conceiving of what’s possible. ‘Can I put in a patch that will get blood from this inlet to this outlet?’ So that will change the operation that you conceive of doing.”
Collaborative Research Outlook
Interdisciplinary collaboration has been a fruitful part of Dr. Hammel’s research program, and one he seeks to keep cultivating. As one example, he and Dr. Kari Simonsen (Pediatric Infectious Diseases) are teaming up for a prospective clinical trial comparing cardiac surgery outcomes in children with and without asymptomatic viral infections. “Within Cardiac, we want to be a strong participant in clinical research, so we want to increase our capacity to self-assess, to look at the outcomes of our own work, and identify things that are good and the things that are still challenging. If you’re doing that, I think you naturally come up with questions you want to look at, whether it is by prospective trials or it’s taking something to the laboratory.”
Dr. Hammel touts surgeons in general as uniquely qualified contributors to research, while acknowledging distinct challenges in their allocation of time for research and publication. “We’re involved with patients over an extended period. I always have babies in the hospital. Any surgeon is always going to be available for their patients and their needs. So protected time is tough.” Still, outweighing the challenges is the greater purpose of making sure discoveries are disseminated to the wider surgery community. “It really is a duty. It’s kind of the price of admission. If you innovate, you have to publish. It’s not ethical to innovate and keep it a secret.”
- Krishnamurthy et al. (2013) Neonatal cardiac care, a perspective. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 16(1):21-31.
- Hammel, JM. (2019) Supplemental perfusion techniques for aortic arch reconstruction, with emphasis on direct cannulation of the descending aorta. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 22:14-20.
- Meier et al. (2017) Structural and congenital heart disease interventions: the role of three-dimensional printing. Neth Heart J. 25(2):65-75.
by Matthew Sandbulte, CHRI Grant Writer | August 6, 2019