It is generally assumed that left ventricular (LV) hypertrophy in aortic stenosis (AS) is a compensatory adaptation to chronic outflow obstruction. The advent of transcutaneous aortic valve replacement has stimulated more focus on AS in older patients, most of whom have antecedent hypertension. Accordingly, our aim was to investigate the interaction between hypertension and AS on LV remodeling in contemporary practice. We studied consecutive patients referred for echocardiograms with initial aortic valve (AV) peak velocity <3.0 m/s and a peak velocity of >3.5 m/s on a subsequent study performed at least 5 years later. LV size and geometry were measured echocardiographically. Midwall fractional shortening (FSmw) and peak systolic stress were calculated from 2-dimensional echocardiographic and Doppler data. Of 80 patients with progressive AS, 59% were women with mean age 82 ± 9 years. The average interval between the 2 echocardiograms was 5.9 ± 1.8 years. During the study period, peak velocity increased from 2.5 ± 0.4 to 4.2 ± 0.6 m/s (p < 0.01) and LV mass indexed to body surface area increased from 80 ± 28 to 122 ± 51 g/m 2 (p < 0.01) with a corresponding shift from normal or concentric LV remodeling geometry to concentric hypertrophy. There was no correlation between change in LV mass index and AV mean gradient or valvulo-arterial impedance. However, change in LV mass index did correlate positively with initial peak velocity and inversely with initial LV mass. Plots of FSmw against circumferential stress at baseline and follow-up suggest that systolic function more than compensates for increasing load in many patients. In conclusion, most patients seen in our practice with severe AS have antecedent hypertension and LV remodeling at a time when outflow obstruction is mild. LV remodeling worsens in parallel with worsening severity of AS. Remodeling in these patients features increasing concentric remodeling of the LV, rather than LV dilation. Systolic function, as assessed by FSmw, remains compensated, or even improves relative to afterload, during progression of AS. Given these findings, we speculate that regression of LV hypertrophy to normal will not be affected by transcutaneous aortic valve replacement because LV hypertrophy preceded hemodynamically severe AS.
It is generally assumed that left ventricular (LV) hypertrophy in AS is a compensatory adaptation to the high LV pressures caused by chronic outflow obstruction. It follows that LV mass regression following aortic valve replacement would be proportional to the reduction in systolic load effected by surgery. Indeed, such a relationship has been shown in the past by numerous investigators in clinical studies. However in contemporary clinical practice, most patients with AS are older than the subjects enrolled in clinical studies published 2 or 3 decades ago, and the majority have coexistent hypertension as well as other comorbidities, such as metabolic syndrome and coronary artery disease. Carroll et al and Antonini et al, among others, have called attention to this “double loaded” LV. , The issue of whether the older, hypertensive LV remodels following aortic valve (AV) intervention is important, especially with the advent of transcutaneous aortic valve replacement (TAVR), which has stimulated more focus on AS in older patients. Accordingly, our aim was to investigate the interaction between hypertension and AS on LV remodeling. The advent of digital echocardiographic archiving and the electronic medical record facilitated analysis of LV remodeling among patients followed with serial echocardiographic studies.
Methods
The digital echocardiography database at UMassMemorial Medical Center was queried for patients with severe AS who had an antecedent echocardiogram in the archive. Our institution serves as a community hospital for the central Massachusetts area, so that serial studies for progression of AS and other valvular diseases are common. Our study population comprised 270 patients who carry a diagnosis of severe AS (AV peak velocity >3.5 m/s) based on transthoracic echocardiogram (TTE) obtained in 2017 to 2018. Of these, 80 patients had a prior TTE that was obtained at least 5 years preceding the diagnosis of severe AS, on which study the AV peak velocity was <3.0 m/s. The University of Massachusetts Medical School Human Subjects Committee approved the study.
Echocardiography, including measurement of LV dimensions, wall thickness, and mass, was performed according to the recommendations of the American Society of Echocardiography by experienced investigators and supervised by a senior echocardiographer. LV ejection fraction was measured using the biplane Simpson’s method. Investigators confirming LV measurements were blinded to AV Doppler measurements and to whether each echocardiogram was the initial or follow-up study.
Relative wall thickness was calculated as the twice the posterior wall thickness divided by the LV end-diastolic diameter; normal relative wall thickness was defined as ≤0.42. LV mass was calculated using the American Society of Echocardiography “cube” formula and indexed to body surface area. LV hypertrophy was defined as LV mass index >95 g/m2 in women and >115 g/m2 in men. The relative wall thickness and gender-specific LV mass index partition values were combined to define 4 patterns of LV morphology: normal by both parameters; eccentric hypertrophy with normal relative wall thickness and increased LV mass index; concentric remodeling with increased relative wall thickness and normal LV mass index; and concentric hypertrophy with both parameters increased.
The peak systolic flow velocity in the LV outflow tract was measured with pulsed wave Doppler and the AV peak velocity was measured with continuous wave Doppler using the acoustic window that produced the highest Doppler velocity. The AV area was calculated using the continuity equation. Valvulo-arterial impedance (Zva, mm Hg/ml/m 2 ), an assessment of global afterload, was calculated as (systolic blood pressure + mean AV transvalvular gradient) ÷ stroke volume index.
Prior work from our laboratory and others have shown that midwall stress-shortening relations provide insight into systolic function when concentric geometry is present by normalizing the circumferential shortening of the myocardium for the increased wall thickness. We computed the midwall fraction shortening (FSmw) using previously published methodology. FSmw, considered an index of regional circumferential function, was plotted against circumferential stress at baseline and at follow-up. We superimposed 95% confidence limits derived from normotensive patients in our laboratory. Intraventricular pressure was used for the estimation of wall stress and was calculated as systolic blood pressure + 0.7 × AV peak gradient.
Continuous data are presented as mean ± standard deviation. Differences between baseline TTE and follow-up TTE data were tested using paired-sample t tests with significant differences evaluated at p < 0.05 . Categorical data are presented as percentages and differences determined using χ2 test . Linear regression models were used to analyze the relations between the change in LV mass index and the change in other structural and echocardiographic parameters.
Results
Table 1 shows the demographic data in the study population. The population was elderly, with high prevalence of coronary artery disease and hypertension. Table 2 shows the echocardiographic data at baseline and follow-up. The mean duration between TTE was 5.9 ± 1.8 years. Over that time, there were significant changes in AS severity, by study design; mean gradient increased, and AV indices became consistent with severe AS. Systolic blood pressure was lower at follow-up than at baseline (131 ± 20 vs 141 ± 18 mm Hg, p ≤ 0.001) but this was offset by the progression of AS so that both intraventricular pressure (179 ± 22 vs 160 ± 20 mm Hg, p < 0.001) and Zva (5.1 ± 2.1 vs 4.2 ± 1.7 mm Hg/mL/m2, p < 0.001) were significantly higher at the follow-up study.
| Variable | Value (%) |
|---|---|
| Age (years) | 82±9 |
| Women | 47 (59) |
| White | 74 (92) |
| Body mass index (kg/m 2 ) | 29±1 |
| Systolic blood pressure (mm Hg) | 143±19 |
| Diastolic blood pressure (mm Hg) | 69±12 |
| Heart rate (bpm) | 67±13 |
| Body surface area (m 2 ) | 2.0±0.3 |
| Hypertension | 65 (81%) |
| Obstructive sleep apnea | 9 (11%) |
| Hyperlipidemia | 54 (68%) |
| Smokers | 37 (46%) |
| Medications | |
| ACE- inhibitors | 18 (22%) |
| Calcium channel blocker | 23 (29%) |
| Diuretics | 35 (44%) |
| Beta blockers | 51 (64%) |
| Variable | Baseline TTE | Follow up TTE | p- value |
|---|---|---|---|
| LV internal dimension, diastole (mm) | 43.8±6.4 | 45.8±8.2 | 0.02 |
| Interventricular septum thickness, diastole (mm) | 12.0±2.6 | 13.4±2.4 | 0.00 |
| Posterior Wall thickness (mm) | 10.4±2.1 | 11.5±2.1 | 0.00 |
| Relative Wall Thickness (mm) | 0.49±0.13 | 0.52±0.12 | 0.06 |
| LV Mass Index (grams/M2) | 80±28 | 122±51 | 0.00 |
| Left Ventricular Ejection Fraction (%) | 61.5±7.9 | 59.4±12.0 | 0.12 |
| LV outflow tract Velocity Time Integral (VTI) (cm) | 23±6 | 21±7 | 0.01 |
| LV peak velocity (M/s) | 2.4±0.4 | 4.2±0.6 | 0.00 |
| Systolic blood pressure (mm Hg) | 141±18 | 131±20 | 0.00 |
| Diastolic blood pressure (mm Hg) | 72±15 | 68±12 | 0.07 |
| AV peak gradient (mm Hg) | 27±9 | 69±15 | 0.00 |
| AV mean gradient (mm Hg) | 15±6 | 43±10 | 0.00 |
| AV area (cm 2 ) | 1.4±0.5 | 0.7±0.2 | 0.00 |
| Intraventricular pressure (mm Hg) | 160±20 | 179±22 | 0.00 |
| Valvulo-arterial impedance (Zva) (mm Hg/mL/M 2 ) | 4.2±1.7 | 5.1±2.1 | 0.00 |
| Circumferential wall stress (g/cm 2 ) | 95.4±41.7 | 191.7±79.9 | 0.00 |
| Midwall fractional shortening (FSmw)(%) | 17.0±5.3 | 14.4±5.2 | 0.00 |
| Prevalence of left ventricular remodeling (n, %) | |||
| Normal geometry | 24 (30%) | 10 (13%) | |
| Concentric remodeling | 38 (48%) | 19 (24%) | |
| Concentric hypertrophy | 14 (18%) | 39 (49%) | |
| Eccentric hypertrophy | 4 (5%) | 12(15%) | |
| Left ventricular hypertrophy (%) | 18 (23%) | 51 (64%) | 0.00 |
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