June 01, 2014
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The next decade of pediatric cardiology and cardiac surgery

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“Never make predictions, especially about the future.” Baseball manager Casey Stengel reportedly offered that advice. We choose to ignore Casey’s rule because forecasting gives us a chance to look both at where we’ve been and where we may be going. Although cardiology and cardiac surgery are, of course, intimately connected, for clarity consider each subspecialty in turn as we look ahead to the next decade’s worth of innovations.

Based on the current status of our field, we can construct a list of near-future developments in pediatric cardiology. By 2024, we can reasonably expect some or all of these:

  • Preconception diagnosis of congenital heart disease.
  • A vaccine for atheroma.
  • Discovery of the cause of Kawasaki disease.
  • A vital implantable valve.
  • A cure for pulmonary hypertension.
  • Myocardial regeneration.
  • Refinements and greater integration of these “dimensions” within the cardiology time-space continuum — clinical practice, the catheterization laboratory, MRI and electrophysiology.

Changes in heart care delivery

Thomas L. Spray, MD 

Thomas L. Spray

Andrew N. Redington, MD 

Andrew N.
Redington

Stepping back from these exciting potential advances, however, a broader view allows us to glimpse some more disruptive organizational and systemic changes in the delivery of heart care.

One such disruptive change is upon us, as the current era of big data and emerging genomic medicine is overturning the traditional randomized clinical trial. The conventional model of performing one experiment (ie, a specific drug or dosage) in 10,000 patients has often faltered in the field of congenital heart disease. A test population of patients with the same diagnosis includes a significant proportion of those who are nonresponders or toxic responders to the intervention being tested. Consequently, even large studies, such as the carvedilol trial for children and adolescents with HF, end up being underpowered, with disappointing results.

An emerging research model reverses the randomized clinical trial approach by conducting 10,000 experiments in one patient. Manipulating an individual patient’s induced pluripotent stem cells, for example, offers the promise of treating vascular abnormalities in Williams-Beuren syndrome. As another example, whole-exome sequencing of patients with rare diseases will enable high-throughput drug screening to pinpoint a therapy specific to an individual patient.

Some disruptive changes ought to happen, but may not. Falling under that rubric, both for pediatric cardiology and for the medical profession as a whole, is a transformation of the fundamental structure of health care delivery. Porter and Teisberg’s proposed value-based health care system describes a 21st-century model of integrated care that goes beyond the incremental improvements provided by quality management, safety initiatives, better disease management and other overlays. This integrated care model envisions a focus on a medical condition or a patient population with common needs; dedicated teams and facilities focused around the patient; gathering providers into the same organizational unit with improved communication; and encompassing inpatient, outpatient and rehabilitation services.

Increased survival

In cardiology, a paramount issue in considering integrated health care is that of providing services for adult patients with congenital heart disease. The steadily increasing survival of congenital heart disease patients has created a growing population of adult patients without a commensurate development of services specific to their needs.

An overwhelming proportion of adult congenital heart disease patients who require heart surgery are operated on by non-congenital heart surgeons. However, compared with procedures performed by congenital heart surgeons, mortality, length of stay and total hospital costs are significantly higher for adult patients undergoing surgery by non-congenital heart surgeons. The ideal congenital heart center would integrate care for congenital heart disease patients across the lifespan, from the fetal period to late adulthood.

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Underlying the growing numbers of adult congenital heart disease patients, of course, is the improvement in survival rates for nearly all types of pediatric heart surgery, driven by advances in surgical techniques and medical management. However, some mortality stubbornly persists — and it is not necessarily the case that most of the remaining mortality correlates with the accuracy of cardiac repair. We can sew the heart together the same way each time, but patient outcomes may be markedly different.

Upcoming surgical innovations

Upcoming innovations in cardiac surgery are unlikely to be “surgical” in the strictest sense. New technologies and new understandings, rather than new techniques, are more likely to further reduce mortality.

Some of those game changers may include better biomaterials for patches and valves; improved Fontan assist devices, which will also de-emphasize the role of heart transplants; stem cell therapies for ventricular dysfunction; and identification of “best practices” to drive consistent, reproducible care, better outcomes and reduced costs.

Role of personalized medicine

Finally, the increased role of personalized medicine, alluded to already in our examples of patient-specific stem cell treatments and pharmacogenomics, will also have an impact on congenital heart disease surgery.

The clearest example of this trend toward personalized medicine in congenital heart disease surgery is in the evolving understanding of postsurgical neurodevelopmental outcomes. Some years ago, a prominent surgeon stated to one of us that “the brains of children with congenital heart disease are normal at birth, and neurodevelopmental problems are the result of their subsequent treatment.” During the last several decades, this prevailing assumption informed emphatic declarations advocating a series of surgical techniques: avoiding deep hypothermic circulatory arrest, achieving the correct blood gas management, maintaining a higher hematocrit, modifying the inflammatory response, or using high-flow normothermic cardiopulmonary bypass, among others. None of these proposed magic bullets has succeeded in preventing neurologic injury.

What we have learned instead is the role of genetic factors that influence risk for neurodevelopmental dysfunction. Genome-wide association studies of patients with pervasive development problems have detected single nucleotide polymorphisms (SNPs) linked to genes involved in cell signaling, neuronal development and other functions that, when perturbed, may play important roles in neuropathology — both before and after infant heart surgeries occur.

Beyond neurodevelopmental effects, other recent research sheds light on genetic factors affecting survival after pediatric heart surgery. For example, a recent study analyzed transplant-free survival in postsurgical congenital heart disease patients with two SNP genotypes: VEGF-A, which has a functional role in vascular remodeling, and SOD2, which has a role in detoxification after oxidative stress. Both SNPs had independent effects, and a genetic risk score tied to the number of risk alleles negatively correlated with rates of transplant-free survival. Investigation of the biological pathways on which either protective or risk-predisposing genes act could lead to novel therapies targeting such pathways.

Innovation that spurs progress

Innovation is an optimistic and positive word, but it may be applied in a misleading fashion. In deciding to adopt new tools and approaches, our job is to properly evaluate technologies and strategies in the light of long-term outcome data, so we can determine which approaches constitute actual progress, as opposed to those that are merely new and different.

Editor’s note: This commentary is based on recent presentations by the authors at the 17th Annual Update in Pediatric and Congenital Cardiology conference in February, organized by The Children’s Hospital of Philadelphia.

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Kinnear C. Stem Cells Transl Med. 2006;2:2-15.
Porter ME. Redefining Health Care, Boston, MA: Harvard Business School Press; 2006.
Shaddy RE. JAMA. 2007;298:1171-1179.
Thomas L. Spray, MD, is chief of cardiothoracic surgery at The Children’s Hospital of Philadelphia. He can be reached at 34th and Civic Center Boulevard, Philadelphia, PA 19104; email: spray@email.chop.edu. Andrew N. Redington, MD, is chief of cardiology at The Hospital for Sick Children (SickKids) in Toronto. He can be reached at 555 University Ave., Toronto, Canada M5G 1X8; email: andrew.redington@sickkids.ca.

Disclosure: The authors report no relevant financial disclosures.