The systemic right ventricle; Risks and outcomes of congestive heart failure

Funding:  American Heart Association

Contact:  Craig Broberg, Portland, OR


The right ventricle (RV) is a key determinant of clinical status and long-term outcome of patients with both congenital and acquired forms of heart disease.  For patients with a systemic right ventricle (RV) due to transposition of the great arteries (TGA) ventricular systolic function is expected to gradually decline and lead to congestive heart failure (CHF). Yet there are wide discrepancies between ventricular and clinical function, raising questions about their relationship.  In some, the RV does not deteriorate as expected.  When it does, there is little to guide clinicians regarding management.  Standard CHF pharmacotherapies and implantable cardiac defibrillators (ICD) have shown little to no desired effects, even when systolic function is very poor. Measuring systemic RV function poses difficulties. Results from heart transplant or mechanical circulatory support (MCS) in adults with congenital heart disease (ACHD), including those with a systemic RV, have raised concerns for patient selection and timing. Existing studies are small with significant limitations. Because of these realities, the National Heart, Lung and Blood Institute and other research groups have listed mechanisms of RV dysfunction and failure among top research priorities.  In this context, systemic RV patients, seen commonly in ACHD referral centers, provide a unique and pressing opportunity to investigate the relationship between function and failure in the pressure-loaded RV.  We have determined that a retrospective study, larger than any previously, is the most economical way forward.  It will provide tools for risk stratification, a core analysis of novel ventricular function metrics, and details of transplant/MCS outcomes, as well as a means for focused future study.  We hypothesize that clinical and imaging endpoints in a large cohort of systemic RV patients can be used to stratify patients’ at risk for CHF and its complications, and shed light on the ventricular-clinical heart failure relationship.

We aim to characterize magnitude of and risks for clinical CHF in adults with a systemic right ventricle (D-TGA after atrial switch palliation or L-TGA) seen at ACHD centers by:

1)         Quantifying the percentage of systemic RV patients who, following an initial assessment, experience a major adverse CHF event (primary outcome) defined as death, aborted sudden death, heart transplant, or MCS, and identify clinical, morphologic, exercise or hemodynamic factors independently predictive of the outcome. 

2)         Determining the percentage of these same patients who develop worsening clinical CHF (secondary outcome) defined as non-elective hospitalization for CHF (assessed by symptoms, elevated BNP or need for diuresis or new ventricular arrhythmia) or referral for advanced CHF therapies and determine clinical, morphologic, echocardiographic, or hemodynamic factors independently predictive of this outcome.

3)         Measuring systemic RV function by reanalysis of previously performed cardiac magnetic resonance (CMR) studies through a core imaging laboratory, including strain quantification, and determine which metrics of systemic RV function or valve function are most predictive of primary and secondary endpoints as defined above.

4)         Reviewing the subset of patients undergoing transplant/MCS to, a) determine risk factors for both 30-day and one year mortality, and b) compare outcome with propensity-matched patients with CHF (as defined in aim 2) who do not undergo transplant/MCS.