We aimed to evaluate the clinical and hemodynamic impact of transcatheter aortic valve implantation in patients with typical low-gradient severe aortic stenosis (LGSAS) and at high operative risk for surgical valve replacement. Prospectively collected clinical and echo Doppler data were retrospectively analyzed in 112 and 86 patients, respectively. Follow-up period was 31 months (21 to 38). Thirty-eight patients died; combined long-term cardiovascular events were identified in 68 patients. The 30-day mortality rate was 2.4% in patients with typical severe aortic stenosis (AS) and 3.3% in patients with LGSAS (p = 1.0). Two-year survival rate was 77 ± 5% for the former (n = 82) and 68 ± 8% for the latter (n = 30; hazard ratio 1.4, 95% confidence interval 0.7 to 2.7 for LGSAS; p = 0.3). Two-year cardiovascular event-free survival rates were 56.5 ± 5.0% and 48.4 ± 9.0%, respectively, (hazard ratio 1.4, 95% confidence interval 0.78 to 2.3 for LGSAS; p = 0.25). Patients with typical severe AS (n = 64) and those with LGSAS (n = 23) demonstrated similar increases in left ventricular ejection fraction and stroke volume (7 ± 10% vs 6 ± 6% and p = 0.67; 12 ± 22% vs 12 ± 16%, p = 0.88, respectively) and reduction in systolic pulmonary artery pressure (5 ± 14 vs 5 ± 9 mm Hg, respectively, p = 0.83). In conclusion, transcatheter aortic valve implantation appears to result in similar hemodynamic and long-term clinical outcomes for high-risk surgical patients with LGSAS as those with typical severe AS.
Current echo Doppler criteria for severe aortic stenosis (AS) include an aortic valve area (AVA) <1.0 cm 2 , a mean pressure gradient (MPG) >40 mm Hg, and a maximal transaortic velocity (V max ) >4.0 m/s. However, many patients with severe AS based on AVA calculations have low transvalvular gradients (e.g., MPG <40 mm Hg) despite a preserved left ventricular ejection fraction (i.e., LVEF >50%). This hemodynamic subset has recently been recognized as a distinct clinical entity and termed low-gradient severe aortic stenosis (LGSAS). The prevalence of LGSAS has been reported to be as high as 30% to 35%. Outcome in symptomatic LGSAS is determined by an AVA irrespective of pressure gradient. Moreover, LGSAS was postulated to present an advanced stage of the disease with poorer prognosis. Transcatheter aortic valve implantation (TAVI) is an effective treatment in patients who have severe AS and increased operative mortality. However, the role of TAVI in patients with LGSAS and high surgical risk has not been established. We sought to determine the clinical and hemodynamic impact of TAVI in patients with symptomatic LGSAS.
Methods
All patients undergoing TAVI at our institution are enrolled in a prospective registry that records procedural information and clinical and echocardiographic data collected at baseline and then at routinely scheduled follow-up visits (at 30 days, 6 months, 12 months, and then at regular 12-month intervals). Suitability and eligibility for TAVI were determined by a team that included an interventional cardiologist, echocardiologists, and a cardiothoracic surgeon. In the present study, we retrospectively evaluated the hemodynamic and clinical outcomes of patients with AS who were considered to be at increased surgical risk (logistic EuroSCORE >10) who underwent TAVI by transfemoral approach for either typical severe AS (n = 82) or LGSAS with preserved LVEF (n = 30). Sixty-four patients with typical severe AS and 24 patients with LGSAS were included in the echocardiographic outcomes analyses.
Excluded were patients with any valvular regurgitation greater than moderate by echocardiography, those with any degree of concomitant valvular stenosis other than AS, unstable patients requiring intravenous vasopressors or diuretics before TAVI, those without interpretable echocardiogram, and patients with LGSAS and an LVEF ≤50%. Also were excluded patients with MPG <40 mm Hg, consistent with low gradient AS, and V max meeting criteria for typical severe AS (i.e., V max >4 m/s).
The study was approved by the institutional ethics committee.
The clinical end points at 30 days were adjudicated according to the Valve Academic Research Consortium–2 recommendations. In addition, we evaluated 1- and 2-year survival rates and cardiovascular event-free survival rates. Cardiovascular events included overall mortality, hospitalization for heart failure, stroke, new-onset atrial fibrillation, syncope, and atrioventricular block occurring after discharge from index hospitalization.
Left ventricular (LV) end-diastolic volume, LV end-systolic volume (LVESV), and LVEF were calculated by Simpson rule or Quinones method. LV stroke volume was calculated as the product of the LV outflow tract’s cross-sectional area and the velocity-time integral (VTI). For determination of relative change in stroke volume, we used the baseline and follow-up VTIs of the pulsed wave signal at the level of the right ventricular outflow (RVO).
Typical severe AS was defined as an AVA <1.0 cm 2 , an MPG >40 mm Hg, and V max >4 m/s. LGSAS was defined as an AVA <1.0 cm 2 , MPG ≤40 mm Hg, V max <4 m/s, and an LVEF >50%. AS severity in patients with LGSAS was validated using at least 1 additional assessment tool. First, AVA planimetry was attempted using transthoracic images to visualize the minimal orifice area. In cases when shadows and reverberation created by valve calcification limited identification of the valve orifice, the ratio of the LV outflow to aortic jet maximum velocity (velocity ratio = V LVO /V AV ) was calculated. When both methods were considered unreliable, AVA planimetry was obtained by transesophageal images. The patients were classified as having LGSAS if the AVA planimetry was <1.0 cm 2 or the velocity ratio was ≤0.25.
Systolic pulmonary artery pressure (SPAP) was estimated as the sum of the right ventricular to the right atrial pressure gradient during systole and the right atrial pressure.
Aortic regurgitation (AR) was assessed using aortography immediately after TAVI. AR severity was graded from 1+ to 4+, according to the classification proposed by Sellers et al in which 1+ indicates minimal regurgitant jet clearing rapidly from the LV with each beat, 2+ moderate opacification of the LV clearing with the subsequent beat, 3+ intense opacification of the LV that is as dense as that of the proximal ascending aorta, and 4+ intense opacification of the LV that is denser than that of the proximal ascending aorta.
Continuous normally distributed parameters are presented as mean ± SD and were compared using the Student or paired t test, as appropriate. Ordinal and/or non-normally distributed data are presented by the median and the first and third quartiles, and they were compared using the Wilcoxon rank sum or Wilcoxon signed-rank test. Categorical data were compared between groups using the chi-square or Fisher’s exact test. To determine the interobserver variability, all measurements were repeated by a second independent observer in 10 randomly selected patients. The interobserver variability is also expressed as the percentage of ratio of the SDs of the differences between the 2 measurements divided by the respective mean values. Unadjusted Cox proportional hazards were used to analyze the association of the presence of LGSAS with mortality rates or the combined outcome rates with the calculation of hazard ratios and confidence intervals. Event distributions were calculated according to the Kaplan-Meier method and compared using the log-rank test. All p values were 2-sided, and values of <0.05 were considered statistically significant. All data were analyzed with the JMP System software, version 8.0 (SAS Institute, Inc, Cary, North Carolina).
Results
From April 2009 to June 2011, 150 consecutive patients with AS underwent transfemoral implantation of a CoreValve prosthesis (Medtronic, Inc. [NYSE: MDT], Minneapolis, Minnesota) at our institution. Clinical outcome analysis was performed in 112 patients. Eighty-six patients were included in the echocardiographic analysis. The reasons for the exclusion of 38 patients from clinical outcome analysis and 24 additional patients from echo Doppler outcome analysis are displayed in Figure 1 .
Baseline clinical and echocardiographic features are presented in Table 1 . Patients with typical severe AS and those with LGSAS were well matched in terms of their clinical characteristics and estimated risk of surgical aortic valve replacement. With respect to the echocardiographic findings at baseline, patients with typical severe AS had greater V max and MPG, smaller AVA, and greater LV stroke volume, whereas patients with LGSAS had smaller LVESV and greater LVEF. There was no significant difference in the rest of the echo Doppler variables. Severity of AS in LGSAS group was verified by planimetry of aortic valve orifice using transthoracic images in 18 patients and by transesophageal images in 4 patients. The AVA in this subgroup was 0.76 ± 0.07 cm 2 . In 8 cases, AS severity, verified by velocity ration (V LVO /V AV ), was 0.22 ± 0.02.
| Variable | Typical Severe AS | LGSAS | p |
|---|---|---|---|
| Clinical characteristics | |||
| Sample size ∗ | 82 | 30 | |
| Age (yrs) | 83.3 ± 4.5 | 83.4 ± 6.0 | NS |
| Men | 35 | 48 | NS |
| Height (cm) | 162 ± 9 | 162 ± 9 | NS |
| Weight (kg) | 70 ± 15 | 70 ± 16 | NS |
| Body mass index (kg/m 2 ) | 27 ± 4 | 27 ± 4 | NS |
| Body surface area (m 2 ) | 1.59 ± 0.39 | 1.59 ± 0.42 | NS |
| Hypertension | 83 | 74 | NS |
| Diabetes mellitus | 25 | 30 | NS |
| Coronary artery disease | 53 | 48 | NS |
| Atrial fibrillation | 17 | 30 | NS |
| NYHA functional class III/IV | 76/24 | 83/17 | NS |
| EuroSCORE | 24 ± 11 | 29 ± 16 | NS |
| Device size 26/29 mm | 44/56 | 52/48 | NS |
| Echo Doppler characteristics | |||
| Sample size † | 64 | 24 | |
| AV maximal velocity (m/s) | 4.7 ± 0.5 | 3.7 ± 0.2 | <0.01 |
| AV MPG (mm Hg) | 54 ± 12 | 32 ± 4 | <0.01 |
| AVA (cm²) | 0.62 ± 0.14 | 0.73 ± 0.09 | 0.01 |
| AVA index (cm²/m²) | 0.42 ± 0.13 | 0.49 ± 0.14 | 0.04 |
| LV mass (g) | 219 ± 60 | 227 ± 59 | NS |
| LV mass index (g/m²) | 142 ± 45 | 143 ± 49 | NS |
| LV end-diastolic volume (ml) | 91 ± 31 | 82 ± 16 | 0.038 |
| LV end-diastolic volume index (ml/m²) | 60 ± 29 | 51 ± 15 | 0.03 |
| LVESV (ml) | 43 ± 22 | 30 ± 11 | <0.01 |
| LVESV index (ml/m²) | 28 ± 18 | 19 ± 11 | <0.01 |
| LVEF (%) | 54 ± 12 | 60 ± 7 | <0.01 |
| LV outflow tract VTI (cm) | 21 ± 6 | 21 ± 4 | NS |
| LV outflow tract diameter (cm) | 2.2 ± 0.1 | 2.0 ± 0.1 | <0.01 |
| LV stroke volume (ml) | 79 ± 18 | 66 ± 13 | 0.01 |
| LV stroke volume index (ml/m²) | 57 ± 13 | 39 ± 10 | 0.01 |
| RV outflow tract VTI (cm) | 20 ± 4 | 20 ± 5 | NS |
| Systolic pulmonary artery pressure (mm Hg) | 43 ± 13 | 41 ± 18 | NS |
| Mitral regurgitation grade 1+/2+ | 42/25 | 52/22 | NS |
| Tricuspid regurgitation grade 1+/2+ | 58/13 | 60/7 | NS |
∗ Sample size for clinical outcome analysis.
Overall, the postprocedural AR grade in patients with typical severe AS and LGSAS was mild (0.9 ± 0.9 vs 0.8 ± 0.9, respectively, p = 0.96). As listed in Table 2 , there was no significant difference in distribution of the AR grade or in the prevalence of an AR grade ≥2+ between the 2 groups.
| AR Grade | Typical Severe Aortic Stenosis (n = 81) | LGSAS (n = 29) | p |
|---|---|---|---|
| 0 | 31 | 13 | NS |
| 1+ | 31 | 10 | NS |
| 2+ | 15 | 4 | NS |
| 3+ | 4 | 2 | NS |
| 4+ | 0 | 0 | — |
| ≥2+ (%) | 23 | 21 | NS |
The median follow-up was 31 months (21 to 38). Three patients died within 30 days of undergoing TAVI. The cause of death in all 3 cases was grade 3+ AR and cardiogenic shock. There was no significant difference in early mortality between patients with typical AS and those with LGSAS (2.4% vs 3.3%, respectively, p = 1.0). A total of 97 TAVI-related 30-day clinical end points were recorded. As listed in Table 3 , there was no significant difference in the TAVI-related 30-day clinical end points between the 2 study groups. A total of 38 patients died during the follow-up period, and in 68 patients, combined cardiovascular events were identified. There was no significant difference in overall survival rate or cardiovascular event-free survival rate between the 2 study groups. The 1-year survival rates for patients with typical AS and those with LGSAS were 86 ± 4% and 87 ± 6%, respectively; 2-year survival rates for patients with typical AS and those with LGSAS were 77 ± 5% and 68 ± 8%, respectively (p = 0.3; Figure 2 ). The hazard ratio for the presence of LGSAS on mortality rates was 1.4 (95% confidence interval 0.7 to 2.7). The 1-year cardiovascular event-free survival rates for patients with typical AS and those with LGSAS were 69 ± 5% and 65 ± 8%, respectively. The 2-year cardiovascular event-free survival rates for patients with typical AS and those with LGSAS were 57 ± 5% and 48 ± 8%, respectively (p = 0.25; Figure 2 ). The hazard ratio for the presence of LGSAS on the cardiovascular events was 1.4 (95% confidence interval 0.8 to 2.3).
| Variable | Typical Severe AS (n = 82) | LGSAS (n = 30) | p |
|---|---|---|---|
| 1-Month clinical end points | |||
| Mortality | 2 | 1 | 1.0 |
| Stroke | 4 | 1 | 1.0 |
| Myocardial infarction | 2 | 0 | 1.0 |
| Bleeding | 11 | 4 | 1.0 |
| Permanent pacemaker | 18 | 7 | 1.0 |
| Major bleeding | 7 | 2 | 1.0 |
| Vascular complications | 19 | 4 | 0.43 |
| Major vascular complications | 2 | 0 | 1.0 |
| Acute kidney injury stage 1 | 12 | 1 | 0.18 |
| Total procedure-related events | 77 | 20 | 0.52 |
| 2-Yr clinical end points | |||
| Mortality | 25 | 13 | 0.41 |
| Cardiovascular mortality | 12 | 5 | 0.77 |
| CHF hospitalization | 13 | 5 | 1.0 |
| Stroke | 5 | 1 | 1.0 |
| New atrial fibrillation | 7 | 2 | 1.0 |
| Syncope | 1 | 1 | 0.47 |
| Atrioventricular block | 3 | 1 | 1.0 |
Echo Doppler assessments were reproducible. The difference between the 2 observers was 1 ± 3 ml for LV end-diastolic volume, 1 ± 4 ml for LVESV, 1 ± 3 mm Hg for tricuspid regurgitation pressure gradient, 3 ± 5 ml for LV stroke volume, and 1 ± 2 cm for RVO VTI (all p >0.1). The ratio of the SDs of the differences between the 2 measurements divided by the respective mean values was 3% for LV end-diastolic volume, 12% for LVESV, 5% for pressure gradient across the tricuspid valve, 6% for LV stroke volume, and 8% for RVO VTI (all p >0.1).
As listed in Table 4 , TAVI resulted in a significant decrease in V max (p <0.01) and MPG (p <0.01). There was a significant increase in LVEF as a result of reduction in the LVESV. RVO VTI, a marker of stroke volume, increased as well, whereas SPAP decreased. As listed in Table 5 , the changes in echo Doppler parameters in the patients with typical severe AS and those with LGSAS were concordant. Table 6 compares the absolute and percent values of the pre- and postprocedural changes in echo Doppler variables between patients with typical severe AS and those with LGSAS. There was nonsignificant difference between the 2 study groups both for absolute and percent change in the variables evaluated in the present study.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
