OHSU

ACHD

Alliance for Adult Research in Congenital Cardiology

alliance-for-adult-research

OHSU is part of the Alliance for Adult Research in Congenital Cardiology, a nascent group createdto plan, fund, and execute much needed multicenter research in ACHD.

 

Research in Adult Congenital Heart Disease (ACHD)

We are studying causes of heart failure in congenital heart disease. Heart failure in patients with adult congenital heart disease (ACHD) is an increasingly common and life-threatening complication for a substantial portion of the over 800,000 ACHD patients nationwide, many of whom die prematurely. There has been little research exploring the etiology of ventricular systolic dysfunction, and therefore treatment options are empiric. Despite likely mechanistic differences with other forms of heart failure, descriptive studies on ACHD highlight some important similarities that can serve as starting points for investigation. There  is evidence that myocardial fibrosis is present, that aldosterone is elevated in serum, and that both correlate with progressive heart failure. An understanding of the complex interplay between fibrosis, aldosterone, and ventricular function is needed to solidify a rationale for specific therapeutic trials in the future.

We have developed a technique for quantifying diffuse, microscopic fibrosis in-vivo using a novel magnetic resonance imaging (MRI)-based approach, which offers much-needed sophistication in studying the progression of this disease. Early work shows evidence of diffuse myocardial fibrosis in several ACHD subgroups, and a correlation with ventricular size. Future work seeks to clarify the etiology of fibrogenesis and the link between fibrosis, aldosteronism, and ventricular function. Such confirmation will be a springboard for future in-depth studies on the specific mechanisms driving fibrosis as well as on the efficacy of targeted pharmacologic interventions.

We are also studying the complexities of cyanotic heart disease, in particular the erythrocytotic response as it relates to hyperviscosity, symptoms, and ventricular function. Cyanosis mandates the presence of secondary erythrocytosis to maintain adequate tissue oxygen delivery. Increased erythropoiesis requires adequate stores of available building blocks for hemoglobin and red blood cells, including iron. However, increased red blood cell volume raises whole blood viscosity and is an unavoidable by-product of secondary erythropoiesis. There is much written, but little known, about the relative balance between necessary erythrocytosis and potential hyperviscosity. Both too little and too much hemoglobin can contribute to symptoms in cyanotic patients. Iron deficiency is a spectrum that in its extreme will sufficiently limit production of hemoglobin and result in lower systemic oxygen transport.