One-Week Postoperative Valvuloarterial Impedance as a Predictor of Left Ventricular Hypertrophy Regression 1 Year After Surgical Aortic Valve Replacement in Patients With Aortic Stenosis

Abstract

Background: Persistent left ventricular hypertrophy (LVH) after surgical aortic valve replacement (SAVR) for aortic stenosis (AS) worsens prognosis. We investigated predictors of LVH regression 1 year after SAVR in AS patients, including patient-prosthesis mismatch (PPM) and valvuloarterial impedance (Zva).

Methods and Results: We retrospectively studied 175 patients who underwent SAVR for AS at Jichi Medical University between 2014 and 2019. Echocardiography was performed at preoperative baseline, 1-week postoperative, and 1-year postoperative. The left ventricular mass index (LVMI) regression rate (RR) was defined as the difference between baseline LVMI and 1-year LVMI divided by baseline LVMI. Patients were divided into 2 groups based on their median LVMI RR as follows: (1) a poor LVH regression (PR-LVH) group with values below the median LVMI RR; and (2) a good LVH regression (GR-LVH) group with values above the median LVMI RR. The median LVMI RR was 25.4%. There were 88 (50.3%) patients in the PR-LVH group. In the multivariable analysis, 1-week postoperative Zva (odds ratio [OR] 2.777; 95% confidence interval [CI] 1.584–4.869; P<0.001) and baseline LVMI per 10-unit increment (OR 0.974; 95% CI 0.960–0.988; P=0.001) were independent predictors of PR-LVH. The receiver operating characteristic curve analysis identified Zva ≥3.5 mmHg/mL/m² as a cut-off value associated with PR-LVH.

Conclusions: One-week postoperative Zva was a better predictor of improved LVH at 1 year after SAVR than PPM.

Chronic elevated afterload due to aortic stenosis (AS) causes concentric left ventricular hypertrophy (LVH).¹ In principle, invasive intervention for valvular AS is necessary to improve LVH in patients with severe AS. It has been reported that a decline in the left ventricular mass index (LVMI) after surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) improves the prognosis of patients with AS.^2,3 However, even after successful aortic valve replacement (AVR), LVH does not always improve. One of the factors associated with persistent LVH after AVR is patient-prosthesis mismatch (PPM).^4,5 PPM occurs when the effective orifice area of a normally functioning prosthesis is too small in relation to the patient’s body size (and therefore cardiac output requirements), resulting in abnormally high postoperative gradients. Several studies have reported that PPM is associated with mortality and poor LVMI regression.^6–8 In contrast, valvuloarterial impedance (Zva) has been proposed as an index of global left ventricular (LV) afterload, and consists of both systemic and valvular loads.⁹ Baseline Zva has been reported to be associated with poor prognosis and symptoms in patients with AS.^10,11 However, baseline Zva does not reflect the hemodynamic improvement achieved by AVR.

The aim of this study was to identify factors influencing LVH regression 1 year after SAVR in patients with AS, focusing on echo parameters after SAVR. In particular, this study examines 1-week postoperative Zva and PPM, which are conventionally recognized to be associated with LVH regression after AVR.

Methods

Study Population

The present study was conducted at Jichi Medical University, Shimotsuke, Japan using a retrospective design. Clinical, operative, echocardiography, and outcome data were collected from a computerized database. We analyzed the data of 320 patients aged >65 years with predominant AS who underwent isolated surgical AVR between January 2014 and December 2019. Patients with moderate or severe valvular disease other than AS were generally excluded. Patients with active infective endocarditis, pacemaker-dependent rhythm, chronic renal insufficiency (serum creatinine ≥2 mg/dL), or poor image quality unsuitable for echocardiography analysis were also excluded from the study. The remaining 214 patients constituted the study group. The study protocol was approved by the Institutional Review Board of Jichi Medical University.

Clinical Data

The clinical data included age, gender, body mass index, documented diagnosis of hypertension, diabetes, hypercholesterolemia (with or without treatment), current smoking, and presence of atrial fibrillation, coronary artery disease or drugs. Following echocardiography, systemic blood pressure was measured in the supine position using a cuff sphygmomanometer.

Echocardiography

Transthoracic echocardiography was performed by 2-dimensional Doppler echocardiography using the Philips iE33 and EPIQ 7 ultrasound systems (Philips Healthcare Ultrasound LLC, Bothell, WA, USA) in clinically stable patients. LV end-diastolic diameter and volume (LVEDV), LV end-systolic diameter and volume (LVESV), LV end-diastolic septal thickness, and LV end-diastolic posterior wall thickness were measured in the parasternal long-axis view. Relative wall thickness (RWT) and LV mass were calculated and indexed to body surface area (LVMI) using the corrected American Society of Echocardiography formula.¹² The LVMI regression rate (RR; %) was calculated as 100 × (LVMI at baseline − LVMI at 1-year after SAVR) / (LVMI at baseline). LVEF was calculated using the biplane method (modified Simpson’s rule).¹² Stroke volume was calculated as the product of LV outflow tract area and velocity-time integral from pulsed-wave Doppler echocardiography of the LV outflow tract and indexed for body surface area (stroke volume index [SVI]).

To assess the severity of AS, peak and mean aortic velocities were obtained by continuous-wave Doppler echocardiography using a multi-window approach, and the corresponding pressure gradients were calculated using the modified Bernoulli equation. Aortic valve area was obtained using the standard continuity equation. Indexed aortic valve area was calculated by dividing the aortic valve area by body surface area. AS was defined as severe if the peak transaortic velocity ≥4 m/s or the mean transaortic pressure gradient was ≥40 mmHg.¹³ In addition, aortic diameters were measured at the level of the sinotubular junction (STJ).¹⁴ The effective orifice area (EOA) was estimated using the formula: EOA (cm²) = LVOT area × (velocity-time integral)_LVOT / (velocity-time integral)_{AS jet}, while the EOA index (EOAI) was calculated using the formula: EOAI (cm²/m²) = EOA/body surface area (BSA). The aortic cross-sectional area (AA) was calculated as π × (aortic diameter/2)². The energy loss coefficient (ELCo) was calculated using the validated formula: ELCo (cm²) = [EOA × AA] / (AA − EOA),^15,16 while the energy loss index (ELI) was calculated using the formula: ELI (cm²/m²) = ELCo/BSA. For prosthetic aortic valves, PPM was classified as ‘severe’ if the EOAI was <0.65 cm²/m² and ‘moderate’ if the value was between 0.65 and 0.85 cm²/m². PPM was classified as not clinically significant if the EOAI was >0.85 cm²/m². To assess diastolic function, peak early diastolic velocity (E) was derived from Doppler recordings of transmitral flow. Peak early diastolic mitral annular velocity (e′) at the lateral site of the mitral annulus was measured using tissue Doppler imaging. The ratio of E to e′ (E/e′) was calculated to estimate the LV filling pressure.¹⁷ Zva was calculated using the formula: Zva (mmHg/mL/m²) = (systolic blood pressure+mean transaortic pressure gradient) / SVI.¹⁸

Follow up

Clinical and echocardiography follow-up data were collected per protocol at baseline (0–7 days before surgery), 1-week postoperative and 1-year postoperative from our electronic medical records. To assess early postoperative hemodynamic changes unaffected by other factors, we used data from echocardiography performed 1 week after surgery.

Statistical Analysis

IBM SPSS Statistics version 27 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Continuous variables are expressed as means±standard deviations and were compared using the Student’s t-test. Categorical variables are expressed as absolute values and frequency percentages and were compared using the chi-squared or Fisher’s exact test as appropriate. Spearman correlation analysis was used to verify the correlation between 1-week postoperative Zva and LVMI RR. The correlation coefficients (r) were deemed statistically significant when the P value was <0.05. Univariable and multivariable logistic regression analyses were performed to identify potential clinical and echocardiography predictors of non-regression of LVH in AS patients 1 year after SAVR after controlling for other potentially confounding factors. Odds ratios (ORs) are presented with 95% confidence intervals (CIs). All parameters predicting non-regression of LVH 1 year after SAVR, with P<0.1 in univariable analysis, were entered into a backward stepwise multivariable regression. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off values of parameters predicting LVH non-regression. An area under the ROC curve (AUC) of >0.7 was considered accurate. Two-tailed P values <0.05 were considered significant.

Results

Clinical Characteristics

Of the 214 patients initially included, 175 (81.8%) had complete follow up with a mean follow-up time of 13±1.1 months postoperative. Patients with a need for additional coronary artery bypass grafting at the time of AVR were not excluded from the study (n=29; 16.6%). We also included cases with a low mean transaortic pressure gradient (<40 mmHg) who were considered clinically to have severe AS and underwent AVR (Supplementary Table 1). Supplementary Table 2 lists the type and size of aortic valve prosthesis of the study patients. The median value of the LVMI RR was 25.4% (interquartile range 11.1–35.2). This median value was used to divide the study population into a good LVH regression (GR-LVH) group (n=87) with LVMI reduction ≥25.4% from baseline to 1 year, and a poor LVH regression (PR-LVH) group (n=88) with a reduction <25.4%. The baseline clinical characteristics of the 175 patients are shown in Table 1. Of the 175 patients (mean age 73.3±7.3 years), 100 (57.1%) were female.

Table 1.

Baseline Clinical Characteristics (n=175)

	Baseline
Age (years)	73.3±7.3
Sex, female	100 (57.1)
BMI (kg/m2)	24.6±4.2
SBP (mmHg)	124.9±19.2
DBP (mmHg)	67.5±12.6
Hypertension	133 (76.0)
Diabetes	55 (31.4)
Hyperlipidemia	111 (63.4)
Current smoking	15 (8.6)
Coronary artery disease	72 (41.1)
Atrial fibrillation	20 (11.4)

Data are presented as n (%), or mean±SD. BMI, body mass index; DBP, diastolic blood pressure; SBP, systolic blood pressure.

Echocardiography Characteristics

Comparisons of echocardiography parameters at baseline, 1 week and 1 year are shown in Table 2. Bioprosthetic valves were implanted in 116 of the 175 patients in this series. All patients had severe AS with a peak transaortic velocity of 4.65±0.76 m/s, mean pressure gradient of 53.0±18.7 mmHg and aortic valve area of 0.63±0.16 cm². LV septal wall thickness, LV posterior wall thickness, LV end-diastolic diameter, LV end-systolic diameter, LVMI and the E/e′ ratio were significantly decreased at 1 year compared with baseline (P<0.05). No significant difference in LVEF was observed 1 year after SAVR compared with baseline. Peak transaortic velocity and mean pressure gradient were significantly reduced at 1 week (P<0.05) and at 1 year (P<0.05). There were no differences in prosthesis-related variables at 1 week vs. 1 year. No significant difference between baseline and 1-year EOAI was observed. Both ELI and Zva significantly decreased at 1 week and at 1 year compared with baseline (P<0.05). No significant differences in ELI or Zva were observed at 1 week vs. 1 year. The type of prosthetic valve used in AVR and the severity of PPM are also shown in Table 2. Severe PPM was observed in 10 (5.7%) patients, and moderate and severe PPM in 66 (37.7%) patients.

Table 2.

Comparison of Echocardiography Parameters at Baseline, 1 Week After SAVR, and 1 Year After SAVR (n=175)

	Baseline	One week after SAVR	One year after SAVR
LV septal wall thickness (mm)	12.9±1.6	12.8±1.5	11.7±2.2*,‡
LV posterior wall thickness (mm)	12.8±1.7	12.8±1.6	11.3±1.6*,‡
LV end-diastolic diameter (mm)	46.0±6.5	45.6±6.4	42.8±5.1*,‡
LV end-systolic diameter (mm)	29.3±7.7	28.9±7.6	26.3±5.1*,‡
LVMI (g/m2)	148.2±36.8	146.8±34.9	112.0±28.1*,‡
LVEF (%)	64.3±12.6	63.7±10.1	66.3±7.1
E/e′	15.9±6.1	14.8±5.6	13.7±5.8*
SVI (mL/m2)	44.3±10.5	38.8±8.8*	45.8±10.4‡
Peak transaortic velocity (m/s)	4.65±0.76	2.45±0.44*	2.48±0.56*
Mean pressure gradient (mmHg)	53.0±18.7	13.1±4.5*	13.7±5.9*
Aortic valve area (cm2)	0.63±0.16
Indexed aortic valve area (cm2/m2)	0.41±0.10
EOAI (cm2/m2)		0.96±0.24	0.95±0.20
ELI (cm2/m2)	0.48±0.14	1.52±0.73*	1.53±1.42*
Zva (mmHg/mL/m2)	4.19±0.98	3.30±0.89*	3.19±0.96*
Bioprosthetic valve		116 (66.2)
PPM grade
Severe		10 (5.7)
Moderate+severe		66 (37.7)

Data are presented as n (%), or mean±SD. *P<0.05 vs. baseline. ^‡P<0.05 vs. 1 week after SAVR. e′, peak early diastolic mitral annular velocity; E, peak early diastolic velocity; ELI, energy loss index; EOAI, effective orifice area index; LV, left ventricular; LVEF, left ventricular ejection fraction; LVMI, left ventricular mass index; PPM, patient-prosthesis mismatch; SAVR, surgical aortic valve replacement; SVI, stroke volume index; Zva, valvuloarterial impedance.

Clinical Data and Echocardiography Parameters Based on LVH Regression

Table 3 compares clinical data and echocardiography parameters of the LVH regression and non-regression groups at baseline, 1 week after SAVR and 1 year after SAVR. At baseline, the PR-LVH group had significantly lower LVMI and RWT, and greater LVEDV, aortic valve area. Systolic blood pressure, LVEF, E/e′, peak transaortic velocity, mean pressure gradient, ELI, Zva and type of drugs used were not significantly different between the 2 groups. No significant difference in the prosthetic valve types used for SAVR was observed between the 2 groups. PPM grade at 1 week postoperative was not significantly different between the 2 groups. One week after SAVR, LVEF and Zva were significantly higher and SVI was significantly lower in the PR-LVH group than in the GR-LVH group. There were no statistically significant differences in peak transaortic velocity, mean pressure gradient, indexed aortic valve area, EOAI, ELI, or drug type. At 1 year after SAVR, RWT, LVMI and Zva were significantly larger and LVEF was significantly smaller in the PR-LVH group. In contrast, the peak transaortic velocity, mean pressure gradient, and EOAI, which were related to valve orifice index, did not significantly differ between the 2 groups. Figure 1 shows the relationship between 1-week postoperative Zva and LVMI RR. The correlation coefficient was statistically significant (ρ=−0.566; P=0.001; Figure 1).

Table 3.

Comparison of Clinical Data and Echocardiography Parameters Based on LVH Regression at Baseline, 1 Week After SAVR and 1 Year After SAVR

	Baseline			One week after SAVR			One year after SAVR
	GR-LVH group (n=87)	PR-LVH group (n=88)	P value	GR-LVH group (n=87)	PR-LVH group (n=88)	P value	GR-LVH group (n=87)	PR-LVH group (n=88)	P value
Age (years)	74.1±6.2	72.6±8.1	0.186
Sex, female	53 (60.9)	47 (53.4)	0.229
BMI (kg/m2)	24.1±4.2	25.1±4.1	0.180
Hypertension	66 (75.9)	67 (76.1)	0.966
Diabetes	30 (34.5)	25 (28.4)	0.419
Hyperlipidemia	53 (60.9)	58 (65.9)	0.532
Current smoking	10 (11.5)	5 (5.7)	0.189
Coronary artery disease	16 (18.4)	13 (14.8)	0.548
Atrial fibrillation	6 (6.9)	10 (11.4)	0.398
SBP (mmHg)	127.0±19.9	124.9±18.4	0.257	124.0±16.0	121.9±12.8	0.157	130.0±22.9	127.9±17.4	0.218
DBP (mmHg)	67.9±12.7	67.1±12.5	0.664	69.9±11.1	67.4±11.8	0.163	73.2±14.2	70.4±11.6	0.167
LVMI (g/m2)	161.9±37.1	135.0±30.7	<0.001	161.2±35.1	134.2±30.0	<0.001	101.4±22.3	125.3±29.0	<0.001
RWT	0.59±0.11	0.56±0.10	0.041	0.58±0.11	0.57±0.10	0.398	0.52±0.10	0.55±0.90	0.032
LVEDV (mL)	88.8±44.6	92.4±42.1	0.043	87.2±44.2	91.5±41.8	0.111	84.2±41.1	88.2±40.4	0.099
LDESV (mL)	32.9±10.6	31.1±10.9	0.410	32.8±11.6	31.2±10.0	0.499	27.9±9.8	30.7±10.5	0.184
LVEF (%)	62.9±13.0	66.3±11.8	0.112	62.4±11.3	65.9±8.2	0.008	67.0±5.71	65.0±8.2	0.015
E/e′	15.7±6.2	14.1±4.6	0.339	15.7±6.2	14.0±4.6	0.101	13.6±5.9	13.5±5.5	0.830
SVI (mL/m2)	44.4±10.7	42.1±10.4	0.510	41.2±9.2	36.4±7.7	<0.001	46.5±10.5	44.5±9.8	0.061
Peak transaortic velocity (m/s)	4.70±0.79	4.61±0.74	0.437	2.45±0.41	2.44±0.47	0.881	2.57±0.46	2.62±0.61	0.382
Mean pressure gradient (mmHg)	54.0±19.3	52.1±18.3	0.508	13.1±4.4	13.0±4.7	0.879	14.0±4.8	14.7±6.3	0.334
Indexed aortic valve area/EOAI (cm2/m2)	0.39±0.10	0.42±0.10	0.150	0.97±0.25	0.95±0.22	0.591	0.91±0.17	0.89±0.15	0.321
ELI (cm2/m2)	0.47±0.14	0.49±0.14	0.294	1.55±0.82	1.49±0.63	0.592	1.49±0.98	1.54±0.56	0.402
Zva (mmHg/mL/m2)	4.18±1.03	4.21±0.93	0.814	3.00±0.77	3.60±0.91	<0.001	3.09±0.88	3.23±0.99	0.033
Bioprosthetic valve				61 (70.1)	55 (62.5)	0.338
Prosthetic valve size (mm)				21.2±1.5	20.0±1.6	0.502
PPM severe				6 (6.9)	4 (4.5)	0.366
Moderate+severe				31 (35.6)	35 (39.8)	0.202
Medication
ACE inhibitors/ARB	58 (66.7)	50 (56.8)	0.214	49 (56.3)	42 (47.2)	0.291
β-blockers	35 (40.2)	44 (50.0)	0.225	72 (82.8)	76 (86.4)	0.537
Calcium channel blockers	32 (36.8)	38 (43.2)	0.441	32 (36.8)	38 (43.2)	0.441
MRAs	10 (11.5)	11 (12.5)	0.838	37 (42.5)	27 (30.7)	0.118
Diuretics	35 (40.2)	35 (39.8)	0.951	35 (40.2)	44 (50.0)	0.225
Statins	44 (50.6)	42 (47.7)	0.763	42 (48.3)	40 (45.5)	0.763

Data are presented as n (%), or mean±SD. ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; GR-LVH, good LVH regression; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic volume; LVH, left ventricular hypertrophy; MRA, mineralocorticoid receptor antagonist; PR-LVH, poor LVH regression; RWT, relative wall thickness. Other abbreviations as in Tables 1,2.

Figure 1.

Correlation of 1-week postoperative valvuloarterial impedance (Zva) with left ventricular mass index (LVMI) regression rate (RR; the percentage change in LVMI from baseline to 1 year after surgical aortic valve replacement).

Predictors of PR-LVH 1 Year After SAVR

In the multivariable analysis, 1-week postoperative Zva (OR 2.777; 95% CI 1.584–4.869; P<0.001) and baseline LVMI per 10-unit increment (OR 0.974; 95% CI 0.960–0.988; P=0.001) were independent predictors of PR-LVH. However, 1-week postoperative EOAI, an indicator of PPM, was not identified as an independent predictor (Table 4). Figure 2 shows the ROC curve for 1-week postoperative Zva in the prediction of PR-LVH. The AUC for 1-week postoperative Zva was 0.76 (95% CI 0.69–0.81; P<0.001). The ROC curve analysis identified Zva ≥3.5 mmHg/mL/m² (sensitivity 73.0%; specificity 72.8%) as the cut-off value associated with PR-LVH (Figure 2).

Table 4.

Univariable and Multivariable Analysis for Prediction of PR-LVH 1 Year After SAVR in Patients With Aortic Stenosis

	Univariable analysis		Backward stepwise multivariable regression
	OR (95% CI)	P value	OR (95% CI)	P value
Age (years)	0.972 (0.932–1.014)	0.188
Female	1.657 (0.901–0.305)	0.118
Baseline LVMI (per 10-unit increment) (g/m2)	0.781 (0.702–0.870)	0.001	0.974 (0.960–0.988)	0.001
Baseline indexed aortic valve area (cm2/m2)	1.408 (0.828–2.870)	0.157
One-week postoperative LVEF (%)	1.049 (1.010–1.085)	0.051
One-week postoperative E/e′	0.946 (0.885–1.011)	0.104
Baseline Zva (mmHg/mL/m2)	1.038 (0.765–1.407)	0.813
One-week postoperative mean pressure gradient (mmHg)	0.995 (0.932–1.062)	0.878
One-week postoperative EOAI×10 (cm2/m2)	0.966 (0.853–1.095)	0.589
One-week postoperative SVI (mL/m2)	0.934 (0.899–0.970)	0.005
One-week postoperative ELI×10 (cm2/m2)	0.988 (0.949–1.031)	0.590
One-week postoperative Zva (mmHg/mL/m2)	2.383 (1.595–3.560)	<0.001	2.777 (1.584–4.869)	<0.001

CI, confidence interval; OR, odds ratio. Other abbreviations as in Table 2.

Figure 2.

Receiver-operating-characteristic curve of 1-week postoperative valvuloarterial impedance (Zva) for the prediction of PR-LVH 1 year after surgical aortic valve replacement (SAVR) in patients with aortic stenosis. AUC, area under curve; PR-LVH, non-regression left ventricular hypertrophy (median LVMI regression from baseline to 1 year after SAVR of ≤25.4%); LVMI, left ventricular mass index.

Discussion

In this retrospective study of 175 consecutive AS patients undergoing SAVR, multivariable analysis showed that 1-week postoperative Zva and low baseline LVMI were predictors of lower-than-average decline in LVMI at 1 year. Notably, 1-week postoperative Zva, but not prosthetic valve-related parameters including EOAI, was associated with a reduction of LVMI at 1 year. Reduced systemic arterial compliance caused by age, hypertension, diabetes, renal disease and atherosclerosis contributes to increased afterload and causes LVH.^19–21 Similarly, increased afterload due to severe AS imposes a very large afterload on the left ventricle.²² Briand et al. found that in patients with AS prior to SAVR, baseline Zva considering both valvular hemodynamic assessment (i.e., ELI) and systemic arterial compliance (SVI/PP) was associated with LV dysfunction rather than either measure of afterload alone.⁹ In patients with AS after SAVR, some studies have shown that PPM is associated with poor LVMI regression,^4,5 but the effect of global afterload on LVMI regression has not been discussed. The present study is important because it fills this gap.

This is the first report to show that poor LVMI regression at 1 year is more strongly associated with 1-week postoperative Zva than with EOAI or ELI. Chen et al. studied postoperative (6 months to 2 years postoperative) hemodynamic parameters including postoperative Zva as a cause of poor LVMI regression in a Taiwanese population.²³ The results revealed that a lower EOAI, presence of PPM, a higher stroke work index, higher mean pressure gradient and higher postoperative LVMI were associated with poor LVMI regression. In Chen et al.’s study, postoperative Zva was not correlated with relative LVMI regression, which is different from the conclusion of the present study. While Chen et al. investigated the association between the relative LVMI regression ratio and each hemodynamic parameter using linear regression analysis, we investigated hemodynamic parameters associated with a median LVMI RR not exceeding 25.4%. The reason why the results of the present study differ from those of Chen et al. may be due to the different methods used to investigate the hemodynamic parameters leading to LVMI regression. The relationship between postoperative Zva and LVH regression and prognostic value should also be considered. Koyama et al. reported that, although based on a small number of cases, ELI was a stronger predictor of LV mass regression 1 year after SAVR with a mechanical valve than EOAI.²⁴ However, in the present study, ELI was not identified as a predictor of LVMI regression at 1 year postoperative. The reason for this discrepancy remains unclear. However, we speculate that differences in the significance of these parameters – specifically, indices focused solely on the assessment of aortic valve position, such as ELI and EOAI, vs. Zva, which reflects global LV afterload – may have influenced the results.

The Placement of Aortic Transcatheter Valves (PARTNER) 3 trial showed that high Zva (≥4 mmHg/mL/m²) and low tricuspid annular plane systolic excursion at 30 days after SAVR and TAVR were significantly associated with a high risk of the primary endpoint (all-cause mortality, stroke, and rehospitalization) at 1 year after AVR, whereas severe PPM was not.²⁵ This study did not evaluate the association between postoperative Zva and LVH regression. In contrast, Chen et al. showed that lower relative LVMI regression was associated with a higher risk of major adverse cardiac or cerebrovascular events.²³ In the present study, high postoperative Zva was associated with poor LVH regression, but due to the retrospective nature of the study and limitations in data collection, we were unable to evaluate the association between postoperative Zva and prognosis. Based on these results, including our study, we speculate that the association between high postoperative Zva and a worse prognosis shown in the PARTNER 3 trial may be due to poor postoperative LVH regression. Although the prevalence of PPM has decreased in SAVR cases,²⁶ the incidence of PPM remains higher in SAVR cases than in TAVR cases.²⁷ The PARTNER 3 trial showed that 30-day postoperative Zva values are also higher in SAVR cases than in TAVR cases.²⁵ Therefore, the impact of postoperative global afterload on the left ventricle is likely to be greater in AS patients treated with SAVR than in those treated with TAVR. Patients with severe AS are now being implanted with improved prosthetic valves with larger EOA than in the past. It is precisely in this new setting that the recognition of factors influencing LVH after SAVR should shift from PPM to postoperative Zva.

Our study showed that baseline Zva was not associated with poor LVMI regression at 1 year. There are several studies on preoperative Zva, but they are mostly related to the natural history of severe AS.^9–11 The prognostic impact of baseline Zva on postoperative survival in patients with severe AS is controversial.^28,29 Our data suggest that it is appropriate to assess LVH regression in AS patients undergoing SAVR with global afterload after SAVR rather than before SAVR. As shown in Table 3, the SVI in the PR-LVH group at 1 week postoperative was significantly lower than that in the GR-LVH group. Possible explanations for the reduced SVI in the PR-LVH group include diminished perioperative preload and myocardial injury resulting from the surgical procedures.³⁰ Furthermore, the PR-LVH group may have exhibited a higher prevalence of cardiomyopathies, including amyloidosis.³¹ Considering these factors related to SVI, it is important to note that the measurement of Zva in the first postoperative week may not purely reflect LV afterload. Additionally, Zva is significantly influenced by the SVI of the denominator parameter due to the structural characteristics of its equation. However, the use of 1-week postoperative SVI for Zva calculation reflects the early hemodynamic changes and afterload conditions, which are crucial for predicting long-term cardiac remodeling. Although influenced by immediate surgical effects, this measure effectively captures the dynamic interplay between afterload reduction and left ventricular adaptation during the recovery period. Furthermore, it is interesting to note that the GR-LVH group, which had a greater tendency for concentric LVH preoperatively, had a significantly greater reduction in RWT at 1 year postoperatively compared with the PR-LVH group. This LV geometric change is likely to have an impact on hemodynamics, including SVI and global LV afterload. Further studies are necessary to validate 1-week postoperative Zva as a reliable indicator of LV afterload following SAVR.

Our results showed that 1-week postoperative Zva >3.5 mmHg/mL/m² predicted poor LVMI regression at 1 year. A previous study showed that Zva >3.5 mmHg/mL/m² at baseline was associated with increased all-cause mortality in AS patients.¹⁰ The 1-week postoperative Zva cut-off values derived in our study are clinically meaningful because they are in close agreement with the results of previous studies. In addition, the PARTNER 3 trial has shown that Zva >4 mmHg/mL/m² after SAVR or TAVR predicts a poor prognosis. We emphasize that our study identifies factors predictive of poor LVMI regression, which is a prelude to poor prognosis caused by high global afterload after SAVR. Adequate antihypertensive treatment of AS patients after AVR is necessary to reduce postoperative Zva. Both the GR-LVH and PR-LVH groups had good blood pressure control 1 week after SAVR, but systolic blood pressure showed a non-significant tendency to be higher in the PR-LVH group than in the GR-LVH group; this relationship persisted at 1 year. The results of this study suggest that aggressive antihypertensive treatment is needed to achieve greater regression of LVMI at 1 year after SAVR, considering that blood pressure is a component of Zva.

In addition to global LV afterload, there are other factors that inhibit LVH regression. The PR-LVH group had a lower LVMI than the GR-LVH group at baseline and a higher LVMI than the GR-LVH group at 1 year. The PR-LVH group experienced only a slight regression in LVMI from baseline to 1 year. There were no significant differences in age, severity of AS or prevalence of obesity, hypertension or diabetes between the GR-LVH and PR-LVH groups. Genetics, cardiac amyloidosis and many other factors contribute to the degree of hypertrophic remodeling in patients with AS.^31,32 In addition to valvular AS, the PR-LVH group may have had these background features leading to LVH, which may have influenced the regression of LVMI.

Study Limitations

The present study has several limitations. First, it has a retrospective design; prospective investigations are needed to verify the ability of 1-week postoperative Zva to predict poor LVMI regression in AS patients after SAVR. Second, we enrolled Japanese AS patients undergoing SAVR at a single institution; our results may not be generalizable to patients in other institutions or in other parts of the world. Third, the number of cases included in this study was small. The statistical power was low, and although there are structural differences and distinct characteristics between bioprosthetic and mechanical valves, we were not able to examine the differences between the 2 or within the specific groups. Fourth, this study includes both classical and paradoxical low-flow low gradient AS (Supplementary Table 1). In this study, we focused only on the postoperative changes in LVMI without considering the geometric pattern of LVH. It cannot be definitively concluded that the geometry pattern of LVH or the hemodynamics of low-flow low-gradient AS do not influence the postoperative changes in LVMI or Zva. Last, we did not follow the medication history of our eligible patients after discharge. Changes in medication history may have influenced this study.

Conclusions

This study suggests that in AS patients after SAVR, 1-week postoperative Zva predicts regression of LVH after SAVR more accurately than PPM or baseline Zva, which have traditionally been associated with LV function and clinical prognosis. In the current era of gradually decreasing PPM in SAVR cases, it is important to evaluate SAVR prognosis and recovery from the perspective of postoperative global afterload.

Sources of Funding

This research received no grant from any funding agency in the public, commercial or not-for-profit sectors.

Disclosures

The authors declare that there are no conflicts of interest.

IRB Information

The present study was approved by the Jichi Medical University and Faculty of Medicine, Ethics Committee (Reference no. A24-007).

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circrep.CR-24-0158

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