The challenge now is to harness this information and understanding into clinical care. As a clinician, I care for an aging population of adults with complex congenital cardiovascular defects. Below, I outline four critical areas that desperately need translation of basic cardiovascular research into solutions for major clinical problems. I frame my expectations for the future in terms of the final common pathologic pathways of congenital cardiovascular malformations and clinical applications of emerging technology.
Arrhythmias are a chronic problem among patients with congenital cardiovascular defects. Many patients with intrinsic and secondary damage to the sinus and/or atrioventricular (a/v) nodes are now treated with electronic pacemakers. In the future, I anticipate that transplantation of biologic pacemakers into the sinus and a/v node will reduce the need for electronic devices. Biologic pacemakers—derived from pacemaker cells and transplanted into appropriate regions of the heart—would reduce the current need for frequent replacements of the battery and pacemaker packs.
Myocardial failure occurs in many patients as the stressed or damaged myocardium is replaced with scar tissue. Currently, we rely on medications to tune the cardiovascular system, reduce myocardial work, and increase cardiac output. For patients who are no longer responsive to medical therapy, heart transplantation is the treatment of last resort. Fetal myocyte transplantation is a promising approach for repairing the myocardium. Embryonic myocytes respond to increased stress with hyperplasia rather than with hypertrophy. Therefore, the goal would be to graft embryonic myocytes to the myocardium where they could proliferate and replace damaged or scarred myocardium.
Pulmonary hypertension is a chronic late complication of high pulmonary artery pressure and flow. Increased wall strain in the pulmonary vascular bed results in medial hypertrophy, reduction of cross-sectional area, and a marked increase in pulmonary vascular resistance. Current medical therapy relies solely on calcium channel blockers, which provide short-term relief from this ongoing complication. Our increased understanding of developmental mechanisms may provide new molecular tools to remodel blood vessel walls, decreasing vascular resistance and, consequently, pulmonary artery pressure.
Valve (a/v or semilunar) failure occurs in many patients with congenital cardiovascular malformations. Current treatment involves surgical replacement with a mechanical or tissue valve. Yet, these valves have a finite life expectancy, resulting in periodic re-replacement. Biomaterial valves are a composite of cells and plastic substrate and hold great promise for tissue compatibility and extended durability. The use of such biomaterial valves seeded with cell lines derived from a patient's own tissue would circumvent many of the problems that result from current replacement valves.
These four areas provide new applications for translating advances in our understanding of cardiovascular development into improvements in the health of our patients. The challenge for both the basic scientist and clinician will be in realizing the fruits of past research labors to impact future clinical care and to improve the quality of life of patients suffering from the ongoing effects of congenital cardiovascular malformations.
During the past 40 years, the field of cardiovascular development has progressed from classic descriptive embryology to cell biology, bioengineering, and the developmental genetics of the heart and blood vessels. An information explosion, stimulated by Connie Weinstein, a series of RFAs and SCOR grants, and the annual Weinstein cardiovascular development meetings, has increased dramatically our understanding of normal and abnormal cardiovascular development.