Better Myocardial Function in Aortic Stenosis with Low Left Ventricular Mass: A Mechanism of Protection against Heart Failure Regardless of Stenosis Severity?

Abstract

About one-tenth to one-third of patients with severe aortic stenosis (AS) do not develop left ventricular hypertrophy (LVH). Intriguingly, the absence of LVH despite severe AS is associated with lower prevalence of heart failure (HF), which challenges the classical notion of LVH as a beneficial compensatory response. Notably, the few studies that have attempted to characterize AS subjects with inadequately low left ventricular (LV) mass relative to LV afterload (i-lowLVM) described better prognosis and enhanced LV performance in AS associated with i-lowLVM, but those reports were limited to severe AS. Our aim was to compare myocardial function between moderate and severe AS with i-lowLVM. We retrospectively analyzed in-hospital records of 225 clinically stable nondiabetic patients with isolated moderate or severe degenerative AS in sinus rhythm, free of coexistent diseases. Subjects with i-lowLVM were compared to those with appropriate or excessive LVM (a/e-LVM), defined on the basis of the ratio of a measured LVM to the LVM predicted from an individual hemodynamic load. Patients with i-lowLVM and a/e-LVM did not differ in aortic valve area, LV end-diastolic diameter (LVd, a measure of LV preload), and circumferential end-systolic LV wall stress (cESS), an estimate of LV afterload. Compared to a/e-LVM, patients with i-lowLVM had increased LV ejection fraction (EF) and especially higher LV midwall fractional shortening (a better index of LV myocardial function than EF in concentric LV geometry) (p < 0.001–0.01), in both moderate and severe AS. LVd and cESS were similar in the four subgroups of the study subjects, i.e., moderate AS with i-lowLVM, moderate AS with a/e-LVM, severe AS with i-lowLVM, and severe AS with a/e-LVM (p > 0.6). Among patients with i-lowLVM, LVM did not differ significantly between moderate and severe AS (p > 0.4), while in those with a/e-LVM, LVM was increased in severe versus moderate AS (p < 0.001). In conclusion, the association of the low-LVM phenotype with better myocardial contractility may already develop in moderate AS. Additionally, cESS appears to be a controlled variable, which is kept constant over AS progression irrespective of LVM category, but even when controlled (by increasing LVM), is not able to prevent deterioration of LV function. Whether improved myocardial performance contributes to favorable prognosis and the preventive effect against HF in AS without LVH, remains to be studied.

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

“…These observations were recently confirmed in an elegant longitudinal study by Ito et al [ 29 ], who observed gradually increasing cESS and falling mwFS in patients with EF < 60% and depressed LV contractility during the progression from moderate to severe AS, while mwFS was unchanged and cESS even slightly decreased over time (by about 6%) in those with EF ≥ 60%. Additionally, in our previous retrospective observational study of nondiabetic AS subjects, we have also reported no significant differences in cESS between moderate and severe AS with EF ≥ 50% [ 11 ]. Accordingly, cESS appears to be a controlled variable in AS subjects with preserved EF, including also P-LFLG-AS.…”

“…We retrospectively pre-screened the dataset of previously described patients with severe symptomatic degenerative AS (aortic valve area (AVA) index ≤ 0.6 cm 2 /m 2 by the continuity equation) and EF ≥ 50% without relevant coexistent diseases and concomitant abnormalities [ 10 , 11 ]. Beyond more than mild aortic regurgitation or disease of another valve, significant (≥50%) epicardial coronary narrowings, a history of acute coronary syndromes or coronary revascularization [ 10 , 11 ], exclusion criteria included any abnormalities which could potentially contribute to low SV index: atrial fibrillation, relevant mitral stenosis, mitral insufficiency or tricuspid regurgitation and right ventricular dysfunction [ 1 ]. We also excluded subjects with diabetes or chronic kidney disease because we had previously demonstrated subtle impairment of LV contractility in AS with concomitant type 2 diabetes [ 12 ] or renal dysfunction [ 13 ].…”

“…Routine echocardiography during the index hospitalization had been performed by an experienced sonographer. From in-hospital echocardiographic records (LV internal diameters and wall thickness) and average in-hospital cuff systolic blood pressure, we calculated LV systolic performance and circumferential systolic wall stress at the midwall level as previously described, assuming a simplified cylindrical two-shell LV model [ 14 , 15 , 16 ], similar to our earlier reports [ 10 , 11 , 12 , 13 ]. The model is based on a constant volume of each of two concentric shells representing the LV myocardium throughout the cardiac cycle and allows the quantification of systolic epicardial migration of a theoretical midwall fiber which is located at the midpoint of the LV wall at end-diastole [ 17 ] ( Figure 1 ).…”