Phenotyping patients with a low-flow, low-gradient aortic stenosis and a preserved ejection fraction undergoing...

In patients undergoing transcatheter aortic valve implantation (TAVI), low flow, low-gradient (LF-LG) often reflects reduced left ventricular ejection fraction (LVEF). However, characteristics and causes of worse outcomes in patients with paradoxical LF-LG and preserved ejection fraction (pEF) remains poorly understood.

To phenotype LF-LG pEF patients using unsupervised echocardiographic clustering.

We included 827 patients undergoing TAVI (UMCG, the Netherlands). LF-LG pEF was defined as LVEF ≥50%, aortic valve area: ≤1.0 cm2, mean gradient <40 mmHg, and a stroke volume index <35 ml/m2. Principal component analysis on 323 AI-assessed echocardiographic parameters (US2.ai) was followed by K-means clustering, with internal (n = 405) and external (n = 173) (TUMunich, Germany) validation.

216/628 patients with complete data (34%) had LF-LG pEF (mean age of 78.8 (± 7.19) years, 57.9% female). Two clusters were identified: cluster 1 (n = 77) showed distinct echocardiographic features related to HFpEF, including larger left and right atrial dimensions (volume, area, length, width, and circumference), and impaired left ventricular global longitudinal strain and a reduced left atrial reservoir strain (across multiple views). They were older and had higher rates of atrial fibrillation (AF) and heart failure (HF), and higher HFpEF scores (49.4% H2FPEF score ≥6 and 71.4% HFA-pEFF score ≥5), versus cluster 2 (n = 139). Cluster 1 had higher 1- and 5-year cardiovascular mortality and HF-hospitalization risk, comparable to that of classical LF-LG patients. Validation reproduced theseresults.

One-third of TAVI patients with LF-LG aortic stenosis have an typical HFpEF/AF phenotype and a poor prognosis. They may benefit from guideline-directed HFpEF therapy, including SGLT-2 inhibitors and MRA.