When medical circumstances are severe and treatment options are limited in number or effectiveness, being able to help patients improve their quality of life (QOL) takes on an elevated importance. To effect changes in QOL, clinical studies should address outcomes that are meaningful to patients, especially for “insidious” diseases that slowly wear them down.
This view recurred among public speakers and expert panelists at a February meeting of the Circulatory System Devices Panel (CSDP) of the Medical Devices Advisory Committee (MDAC), US Food and Drug Administration (FDA). The meeting concerned a premarket approval application (PMA) submission by Abbott Medical (Abbott) for the use of its TriClip G4 System (TriClip), which was proposed to improve the health status in a particular population of patients with symptomatic severe tricuspid regurgitation (TR). These patients were being treated with optimal medical therapy, were at intermediate or greater risk for surgery, and were determined by a heart team to be suitable candidates for tricuspid valve (TV) transcatheter edge-to[1]edge repair (TEER).
TR occurs when the TV leaflets do not close completely during systole, the part of the cardiac cycle when the heart muscle contracts and pumps blood from the chambers into the arteries. Consequently, there is leakage or “regurgitation” of blood from the right ventricle into the right atrium. TR may lack symptoms, or the symptoms are vague (e.g., weakness, fatigue), the American Heart Association (AHA) states.
In the US, the treatment options for patients with severe TR are limited. As presented at the February meeting, these individuals experience debilitating symptoms that impact QOL. Medical therapy is largely driven by diuretic use to manage volume overload; however, it is often ineffective, particularly if diuretic resistance develops. While isolated TV surgery is an option, it is not commonly performed due to the high rate of operative mortality. In a study that evaluated patients aged >18 years who underwent TV repair or replacement from 2004 to 2013, operations per year increased from 290 in 2004 to 780 in 2013.1 Despite this increase in surgical volume, in-hospital mortality was 8.8% and remained unchanged over the study period. The FDA highlighted that most patients with moderate or severe TR are not offered surgery.
Classification of Health Status
To evaluate the impact on QOL, Abbott’s pivotal study of TriClip incorporated a patient-reported outcome (PRO) measure, the Kansas City Cardiomyopathy Questionnaire (KCCQ), in the primary endpoint of its pivotal trial, TRILUMINATE. For the randomised cohort, the endpoint was a hierarchical composite comprising time to all-cause mortality or TV surgery, number of heart failure (HF) hospitalisations, and a ≥15-point improvement in KCCQ overall summary score from baseline at 12 months. A self-administered PRO, the KCCQ evaluates the health status of patients with HF, relying on several domains (e.g., QOL, social limitation, physical function, symptom stability) and two summary scores.
