Impaired Left Ventricular Circumferential Midwall Systolic Performance Appears Linked to Depressed Preload, but Not Intrinsic Contractile Dysfunction or Excessive Afterload, in Paradoxical Low-Flow/Low-Gradient Severe Aortic Stenosis.

Paradoxical low-flow/low-gradient aortic stenosis (P-LFLG-AS) occurs in about one-third of patients with severe AS and preserved left ventricular (LV) ejection fraction (EF). Our aim was to differentiate between altered LV loading conditions and contractility as determinants of subtle LV systolic dysfunction in P-LFLG-AS. We retrospectively analyzed medical records of patients with isolated severe degenerative AS and preserved EF (30 subjects with P-LFLG-AS and 30 patients with normal-flow/high-gradient severe AS (NFHG-AS)), without relevant coexistent diseases (e.g., diabetes, coronary artery disease and chronic kidney disease) or any abnormalities which could account for a low-flow state. Patients with P-LFLG-AS and NFHG-AS did not differ in aortic valve area index and most clinical characteristics. Compared to NFHG-AS, subjects with P-LFLG-AS exhibited smaller LV end-diastolic diameter (LVd) (44 ± 5 vs. 54 ± 5 mm, p < 0.001) (consistent with lower LV preload) with pronounced concentric remodeling, higher valvulo-arterial impedance (3.8 ± 1.1 vs. 2.2 ± 0.5 mmHg per mL/m2, p < 0.001) and diminished systemic arterial compliance (0.45 ± 0.11 vs. 0.76 ± 0.23 mL/m2 per mmHg, p < 0.001), while circumferential end-systolic LV midwall stress (cESS), an estimate of afterload at the LV level, was similar in P-LFLG-AS and NFHG-AS (175 ± 83 vs. 198 ± 69 hPa, p = 0.3). LV midwall fractional shortening (mwFS) was depressed in P-LFLG-AS vs. NFHG-AS (12.3 ± 3.5 vs. 14.7 ± 2.9%, p = 0.006) despite similar EF (61 ± 6 vs. 59 ± 8%, p = 0.4). By multiple regression, the presence of P-LFLG-AS remained a significant predictor of lower mwFS compared to NFHG-AS upon adjustment for cESS (β ± SEM: −2.35 ± 0.67, p < 0.001); however, the significance was lost after further correction for LVd (β = −1.10 ± 0.85, p = 0.21). In conclusion, the association of P-LFLG-AS with a lower cESS-adjusted mwFS, an index of afterload-corrected LV circumferential systolic function at the midwall level, appears secondary to a smaller LV end-diastolic cavity size according to the Frank−Starling law. Thus, low LV preload, not intrinsic contractile dysfunction or excessive afterload, may account for impaired LV circumferential midwall systolic performance in P-LFLG-AS.