Abstract
Objectives.
To evaluate the association between pre-procedure left ventricular hypertrophy (LVH) patterns and clinical outcomes after transcatheter aortic valve replacement (TAVR).
Background.
The association between pre-procedure LVH pattern and severity and clinical outcomes after TAVR is uncertain.
Methods.
Patients (n=31,199) across 422 sites who underwent TAVR from November 2011 through June 2016 as part of the STS/ACC Transcatheter Valve Therapies Registry linked with the Centers for Medicare and Medicaid database were evaluated by varying LVH patterns, according to sex-specific cutoffs for left ventricular mass index (LVMI) and relative wall thickness (RWT). The association between LVH pattern (concentric remodeling, concentric LVH, and eccentric LVH) and outcomes (rates of mortality, myocardial infarction (MI), stroke, new dialysis requirement) at one-year follow-up were evaluated using multivariable hazard models.
Results.
There were no significant associations between concentric remodeling [death: adjusted hazards ratio (HR) 1.03 (95% confidence interval 0.93–1.14), MI: HR 1.06 (0.76–1.47), stroke: HR 1.11 (0.89–1.39), new dialysis: HR 0.86 (0.64–1.15)], concentric LVH [death: HR 1.04 (0.95–1.15), MI: HR 1.12 (0.82–1.52), stroke: HR 1.14 (0.92–1.41), new dialysis: HR 1.17 (0.90–1.51)], or eccentric LVH [death: HR 0.98 (0.87–1.11), MI: HR 1.07 (0.71–1.63), stroke HR 1.01 (0.78–1.32), new dialysis: HR 1.25 (0.92–1.70)] and outcomes at one-year when compared with patients without LVH.
Conclusions.
In a contemporary cohort of patients who underwent TAVR, pre-procedure LVH according to LVMI and RWT was not associated with adverse outcomes at one-year follow-up. TAVR is likely to benefit patients with severe AS regardless of the presence of LVH.
Keywords: aortic stenosis, transcatheter aortic valve replacement, left ventricular hypertrophy
Condensed Abstract
The Transcatheter Valve Therapies Registry was used evaluate the association between pre-procedure left ventricular hypertrophy (LVH) and outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). A total of 31,199 patients were stratified into the following groups: normal, concentric remodeling, concentric LVH, and eccentric LVH based on left ventricular mass index and relative wall thickness. Patients were further stratified by LVH severity. Outcomes included death, myocardial infarction, stroke, and new dialysis requirement. No significant differences were observed between study groups at one-year follow-up. Thus, TAVR is likely to benefit patients with severe AS regardless of LVH severity or pattern.
BACKGROUND
Left ventricular hypertrophy (LVH) develops as a compensatory mechanism to maintain cardiac output and reduce wall stress against increasing left ventricular (LV) afterload in patients with hypertension (1) and aortic stenosis (AS) (2). However, progressive LVH can become maladaptive and lead to myocardial fibrosis and cardiac dysfunction (3)(4). Moreover, LVH, as determined by LV mass (LVM) or LV mass index (LVMI), is an independent predictor of adverse cardiovascular events and mortality in patients with hypertension (5)(6), AS (7)(8), and individuals without cardiovascular disease (9)(10).
In patients with AS who underwent surgical aortic valve replacement (SAVR), pre-operative LVH was associated with an increased risk of adverse in-hospital outcomes and mortality (11)(12)(13)(14). However, a more contemporary study demonstrated no difference in outcomes between patients with and without pre-operative LVH who underwent aortic valve replacement either surgically or via a transcatheter approach (15). These studies are limited by relatively small sample sizes, and none focused exclusively on patients who underwent transcatheter aortic valve replacement (TAVR).
This study aims to investigate further the association between pre-procedure LVH severity and pattern, determined by sex-specific cutoffs for LVMI and relative wall thickness (RWT), and clinical outcomes up to one-year after TAVR in a large cohort of real-world patients using the Society of Thoracic Surgeons/American College of Cardiology (STS/ACC) Transcatheter Valve Therapies (TVT) Registry.
METHODS
Data Source
The design, structure, and data element details of the TVT Registry have been previously published (16). Briefly, the TVT Registry was launched jointly in 2011 by the STS and ACC and includes data on nearly all commercial TAVR procedures done in the United States. Participating centers use standardized definitions to collect clinical information on consecutive TAVR cases including patient demographics, comorbidities, functional status, quality-of-life indices, procedural details, and outcomes. Annual data quality checks are implemented at the National Cardiovascular Data Registry data warehouse and the Duke Clinical Research Institute analysis center, including data quality feedback reports and data range and consistency checks. The full data collection form and accompanying definitions can be accessed at the TVT Registry website (17). The TVT Registry has been linked to the Centers for Medicare and Medicaid Services (CMS) administrative claims database, which allows ascertainment of one-year patient outcomes (18). The Chesapeake Research Review Incorporated institutional review board approved registry activities, and the Duke University institutional review board granted a waiver of informed consent for this study.
Study Population
Patients who underwent TAVR for severe, degenerative AS from November 2011 to June 2016 were included. Patients were excluded if they had non-degenerative aortic valve disease, prior SAVR or TAVR, an aborted procedure, non-Medicare insurance, missing information required for calculation of left ventricular mass index (LVMI) or relative wall thickness (RWT), age less than 65 years, or were ineligible to be linked to CMS claims data.
The TVT Registry includes LV internal diastolic dimension (LVDD), septal wall thickness (SWT), posterior wall thickness (PWT), patient height (H), and patient weight (W) measurements. Using these values, the LVMI was calculated for each patient using the Devereux formula (19) as follows:
Where BSA denotes body surface area in m2. The RWT was calculated for each patient as follows:
The cohort was then stratified into study groups based on sex-specific cutoffs for LVMI and RWT based on American Society of Echocardiography recommendations (20). Study groups included: normal (LVMI ≤ 115 (male) or ≤ 95 (female); RWT ≤ 0.42), concentric remodeling (LVMI ≤ 115 (male) or ≤ 95 (female); RWT > 0.42), concentric LVH (LVMI > 115 (male) or > 95 (female); RWT > 0.42), and eccentric LVH (LVMI > 115 (male) or > 95 (female); RWT ≤ 0.42). Patients with LVH were further stratified into mild concentric LVH, moderate concentric LVH, severe concentric LVH, mild eccentric LVH, moderate eccentric LVH, and severe eccentric LVH study groups (Table 1).
Table 1.
Study group definitions – Sex-specific LVMI and RWT cutoffs based on American Society of Echocardiography recommendations.
| Study Group | LVMI (male) | LVMI (female) | RWT |
|---|---|---|---|
| Normal | ≤ 115 | ≤ 95 | ≤ 0.42 |
| Concentric remodeling | ≤ 115 | ≤ 95 | > 0.42 |
| Mild concentric LVH | 116 – 131 | 96 – 108 | > 0.42 |
| Moderate concentric LVH | 132 – 148 | 109 – 121 | > 0.42 |
| Severe concentric LVH | ≥ 149 | ≥ 122 | > 0.42 |
| Mild eccentric LVH | 116 – 131 | 96 – 108 | ≤ 0.42 |
| Moderate eccentric LVH | 132 – 148 | 109 – 121 | ≤ 0.42 |
| Severe eccentric LVH | ≥ 149 | ≥ 122 | ≤ 0.42 |
Abbreviations: LVH – left ventricular hypertrophy; LVMI – left ventricular mass index; RWT – relative wall thickness.
Study Outcomes
Outcomes were evaluated at hospital discharge and at one-year follow-up using TVT Registry data and CMS claims data, respectively. In-hospital outcomes included: death, myocardial infarction (MI), conduction disturbance requiring permanent pacemaker (PPM) placement, stroke (composite of ischemic stroke, hemorrhagic stroke, and undetermined stroke), and new dialysis requirement. Hospital length of stay and number of hours in an intensive care unit were also evaluated. One-year outcomes included death, MI, stroke (composite of ischemic stroke, hemorrhagic stroke, and undetermined stroke), new dialysis requirement, and aortic valve re-intervention (see Table S1 for relevant billing codes).
Statistical Analysis
Baseline characteristics are summarized as frequency (proportion) for categorical variables and median (interquartile range) for continuous variables. Differences in categorical variables were assessed across study groups using Pearson chi-square tests, while differences in continuous variables were assessed across study groups using rank-based means score statistic (Kruskal-Wallis equivalent). All tests treated subgroups as a nominal variable. All statistical analyses were performed using SAS software (version 9.4, SAS Institute, Cary, NC). Two tailed p-values <0.05 were considered as statistically significant.
Two separate analyses were performed for each outcome. Primary analyses evaluated the association between pre-procedure LVH patterns (concentric remodeling, concentric LVH, and eccentric LVH) and outcomes, while secondary analyses evaluated the association between pre-procedure LVH severity and outcomes.
Logistic regression models were used to examine the relationship between study groups and in-hospital outcomes. Associations between study groups and in-hospital MI were unable to be evaluated as there were too few events (n = 114) in the overall cohort. The Generalized Estimating Equation method with exchangeable working correlation structure was used to account for within hospital clustering. Unadjusted and adjusted odds ratios with 95% confidence intervals (CI) and p-values are provided for all in-hospital outcomes.
A Cox proportional hazards model was used to assess the relationship between study groups and one-year death. For all other one-year outcomes, Fine and Gray’s proportional sub-distribution hazards model was used to account for the competing risk of death. The marginal model approach was used to account for hospital clustering. Kaplan-Meier curves for one-year death and cumulative incidence curves for all other one-year outcomes are provided, with appropriate p-values for log-rank test and Gray’s test. The covariates used for model adjustment included: age, sex, body mass index, hemoglobin, platelet count, serum creatinine, current dialysis, diabetes mellitus, prior MI, prior coronary artery bypass grafting, number of diseased coronary arteries, prior percutaneous coronary intervention, current PPM, previous implantable cardioverter defibrillator, heart failure within two weeks, New York Heart Association class within two weeks, LV ejection fraction (LVEF), tricuspid insufficiency, mitral insufficiency, aortic insufficiency, aortic valve mean gradient, atrial fibrillation/flutter, peripheral arterial disease, prior stroke, prior transient ischemic attack, carotid stenosis, home oxygen use, chronic lung disease, current/recent smoking, porcelain aorta, hostile chest, and valve sheath access site.
RESULTS
Study Population
Between November 2011 and June 2016, 72,249 patients underwent TAVR across 457 clinical sites in the TVT Registry. A total of 28,099 patients were excluded due to missing wall dimension data for LVMI or RWT calculations (n = 12,234), non-Medicare insurance (n = 6,683), non-degenerative aortic valve disease etiology (n = 4,046), valve-in-valve procedures (n = 3,502), or other reasons (n = 1,634). Of the remaining 44,150 patients, 31,199 patients across 422 clinical sites were successfully linked to CMS claims data and formed the final analytic cohort (Figure 1) (see Table S2 for baseline characteristics of overall, excluded, and included patients). Normal LV geometry was present in 3,192 (10.2%) of patients, and 8,791 (28.2%) had concentric remodeling. A total of 19,216 (61.6%) patients had LVH. Of these, 15,421 (80.3%) had concentric LVH and 3,795 (19.7%) had eccentric LVH.
Figure 1.
Study Cohort – Flow diagram depicting derivation of analytic cohort.
Baseline patient characteristics stratified by LVH pattern are shown in Table 2. Most baseline characteristics and co-morbidities had statistically significant differences between study groups. Though the overall sex distribution was nearly even (48.5% female vs 51.5% male), there were significant differences in sex distribution across varying LVH patterns. There were more females with concentric LVH (56.8% vs 43.2%), and more males in the normal (64.9% vs 35.1%), concentric remodeling (58.5% vs 41.5%), and eccentric LVH (58.1% vs 41.9%) groups. Patients with eccentric LVH had higher rates of coronary revascularization, prior MI, PPM implantation, and implantable cardioverter-defibrillator implantation. Patients with eccentric LVH also had the lowest LVEF and higher rates of valvular regurgitation. STS risk score was highest in patients with eccentric LVH (7.5%), followed by concentric LVH (6.9%), normal LV geometry (6.5%), and concentric remodeling (6.0%). Baseline characteristics of patients stratified by LVH severity are shown in Table S3.
Table 2.
Patient characteristics – baseline patient characteristics by study group.
| Overall (n=31,199) |
Normal (n=3192) |
Concentric Remodeling (n=8791) |
Concentric LVH (n=15421) |
Eccentric LVH (n=3795) |
p Value |
|
|---|---|---|---|---|---|---|
| Clinical Characteristics | ||||||
| Age (years) | 84 (79–88) | 83 (78–87) | 84 (79–88) | 84 (79–88) | 83 (77–87) | <0.001 |
| Female | 15116 (48.5) | 1121 (35.1) | 3648 (41.5) | 8757 (56.8) | 1590 (41.9) | <0.001 |
| Black/African American | 911(2.9) | 81(2.5) | 222(2.5) | 522(3.4) | 86(2.3) | <0.001 |
| Hispanic or Latino Ethnicity | 824(2.6) | 81(2.5) | 187(2.1) | 438(2.8) | 118(3.1) | 0.002 |
| BMI (kg/m2) | 26.8 (23.6–31.0) | 26.5 (23.4–30.3) | 26.8 (23.7–30.8) | 26.9 (23.6–31.4) | 26.6 (23.5–30.8) | <0.001 |
| Hemoglobin (g/dL) | 11.8 (10.5–13.0) | 11.9 (10.6–13.1) | 12.1 (10.8–13.3) | 11.7 (10.4–12.9) | 11.7 (10.4–13.0) | <0.001 |
| Creatinine (mg/dL) | 1.1 (0.9–1.4) | 1.1 (0.9–1.5) | 1.1 (0.9–1.4) | 1.1 (0.9–1.4) | 1.2 (0.9–1.6) | <0.001 |
| Left Ventricular Mass Index | 115 (93.1–140.7) | 87.8 (74.9–100.0) | 87.1 (75.0–97.8) | 133.5 (118.1–156.0) | 134.2 (119.6–155.7) | <0.001 |
| Relative Wall Thickness | 0.5 (0.4–0.6) | 0.4 (0.3–0.4) | 0.6 (0.5–0.7) | 0.6 (0.5–0.7) | 0.4 (0.3–0.4) | <0.001 |
| Hypertension | 28191 (90.4) | 2853 (89.4) | 7939 (90.3) | 14003 (90.8) | 3396 (89.5) | 0.021 |
| Current dialysis | 1204 (3.9) | 116 (3.6) | 202 (2.3) | 688 (4.5) | 198 (5.2) | <0.001 |
| Diabetes mellitus | 11247 (36.0) | 1157 (36.2) | 2997 (34.1) | 5700 (37.0) | 1393 (36.7) | <0.001 |
| PAD | 9948 (31.9) | 1052 (33.0) | 2711 (30.8) | 4833 (31.3) | 1352 (35.6) | <0.001 |
| Prior stroke | 3785 (12.1) | 330 (10.3) | 1066 (12.1) | 1935 (12.5) | 454 (12.0) | 0.006 |
| Prior TIA | 2883 (9.2) | 293 (9.2) | 867 (9.9) | 1414 (9.2) | 309 (8.1) | 0.022 |
| Carotid stenosis | 6485 (20.8) | 681 (21.3) | 1838 (20.9) | 3142 (20.4) | 824 (21.7) | 0.077 |
| Home oxygen | 3695 (11.8) | 376 (11.8) | 1033 (11.8) | 1835 (11.9) | 451 (11.9) | 0.986 |
| Chronic lung disease, moderate/severe | 8395 (26.9) | 899 (28.2) | 2325 (26.4) | 4091 (26.5) | 1080 (28.5) | 0.027 |
| Current/recent smoking | 1380 (4.4) | 153 (4.8) | 364 (4.1) | 654 (4.2) | 209 (5.5) | 0.002 |
| CAD, number of diseased vessels | <0.001 | |||||
| 0 | 11218 (36.0) | 1021 (32.0) | 3287 (37.4) | 5765 (37.4) | 1145 (30.2) | |
| 1 | 6302 (20.2) | 599 (18.8) | 1858 (21.1) | 3164 (20.5) | 681 (17.9) | |
| 2 | 5054 (16.2) | 534 (16.7) | 1418 (16.1) | 2460 (16.0) | 642 (16.9) | |
| 3 | 8396 (26.9) | 1013 (31.7) | 2177 (24.8) | 3910 (25.4) | 1296 (34.2) | |
| Prior MI | 7853 (25.2) | 926 (29.0) | 1825 (20.8) | 3743 (24.3) | 1359 (35.8) | <0.001 |
| Prior PCI | 11289 (36.2) | 1292 (40.5) | 3124 (35.5) | 5331 (34.6) | 1542 (40.6) | <0.001 |
| Prior CABG | 8460 (27.1) | 1071 (33.6) | 2136 (24.3) | 3843 (24.9) | 1410 (37.2) | <0.001 |
| PPM | 5256 (16.8) | 531 (16.6) | 1349 (15.3) | 2640 (17.1) | 736 (19.4) | <0.001 |
| Prior ICD | 1300 (4.2) | 195 (6.1) | 156 (1.8) | 478 (3.1) | 471 (12.4) | <0.001 |
| NYHA Class III/IV | 25389 (81.4) | 2574 (80.6) | 6900 (78.5) | 12712 (82.4) | 3203 (84.4) | <0.001 |
| Hostile chest | 2166 (6.9) | 274 (8.6) | 615 (7.0) | 983 (6.4) | 294 (7.7) | <0.001 |
| Porcelain aorta | 1634 (5.2) | 154 (4.8) | 472 (5.4) | 828 (5.4) | 180 (4.7) | 0.282 |
| AF/FL | 13341 (42.8) | 1345 (42.1) | 3673 (41.8) | 6633 (43.0) | 1690 (44.5) | 0.026 |
| STS risk score | 6.7 (4.4–10.3) | 6.5 (4.2–10.1) | 6.0 (4.0–9.0) | 6.9 (4.6–10.6) | 7.5 (4.9–11.7) | <0.001 |
| Echocardiographic Characteristics | ||||||
| LVEF (%) | 58 (47–60) | 55 (40–60) | 60 (55–60) | 58 (50–60) | 43 (30–57) | <0.001 |
| AV mean gradient (mmHg) | 42 (35–51) | 40 (32–47) | 42 (35–49) | 44 (37–54) | 40 (31–48) | <0.001 |
| Mitral regurgitation, moderate/severe | 9452 (35.4) | 915 (34.0) | 1972 (26.7) | 4952 (37.2) | 1613 (48.6) | <0.001 |
| Tricuspid regurgitation, moderate/severe | 7855 (25.2) | 808 (25.3) | 2029 (23.1) | 3937 (25.5) | 1081 (28.5) | <0.001 |
| Aortic regurgitation, moderate/severe | 5755 (18.4) | 550 (17.2) | 1297 (14.8) | 3048 (19.8) | 860 (22.7) | <0.001 |
| Valve sheath access site | 0.006 | |||||
| Femoral | 24554 (78.7) | 2537 (79.5) | 7013 (79.8) | 12055 (78.2) | 2949 (77.7) | |
| Non-femoral | 6617 (21.2) | 653 (20.5) | 1767 (20.1) | 3357 (21.8) | 840 (22.1) |
Values are median (25th – 75th percentile) or n (%).
Abbreviations: AF/FL – atrial fibrillation/flutter; AV – aortic valve; BMI – body mass index; CABG – coronary artery bypass grafting; CAD – coronary artery disease; ICD -- implantable cardioverter defibrillator; LVEF – left ventricular ejection fraction; MI – myocardial infarction; NYHA – New York Heart Association; PAD – peripheral arterial disease; PCI – percutaneous coronary intervention; PPM – permanent pacemaker; STS – Society of Thoracic Surgeons; TIA – transient ischemic attack
In-Hospital Outcomes
In-hospital outcomes for the overall study cohort included death (3.1%), MI (0.4%), conduction disturbance requiring PPM placement (11.0%), stroke (1.9%), and new dialysis requirement (1.3%). Rates of in-hospital outcomes stratified by LVH pattern and severity are shown in Table S4.
The associations between LVH patterns and in-hospital outcomes are shown in Table 3. There were no significant associations between varying LVH patterns and in-hospital outcomes, except for lower adjusted odds of conduction disturbance requiring PPM placement in the concentric remodeling group, when compared with the normal group (OR 0.84 95% CI 0.72 – 0.99) (Table 3b). When groups were stratified by LVH severity, only patients with moderate eccentric LVH had lower odds of in-hospital death (OR 0.59 95% confidence interval [CI] 0.37 – 0.93) compared with the normal group. The associations between varying degrees of LVH severity and other in-hospital outcomes were not significant (Table S5).
Table 3.
Risk of in-hospital clinical outcomes by LVH pattern – (a) Unadjusted and (b) adjusted in-hospital clinical outcomes comparing concentric remodeling, concentric LVH, and eccentric LVH groups to the normal group (reference).
| (a) |
| Outcome | Concentric Remodeling (n=8791) |
Concentric LVH (n=15,421) |
Eccentric LVH (n=3795) |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Number (%) | OR (95% CI) | p Value | Number (%) | OR (95% CI) | p Value | Number (%) | OR (95% CI) | p Value | |
| Death | 261 (3.0) | 0.86 (0.70–1.06) | 0.165 | 487 (3.2) | 0.92 (0.75–1.12) | 0.395 | 117 (3.1) | 0.91 (0.70–1.18) | 0.459 |
| PPM Requirement | 800 (10.7) | 0.95 (0.80–1.12) | 0.522 | 1476 (9.6) | 1.03 (0.88–1.20) | 0.716 | 316 (8.3) | 0.86 (0.70–1.05) | 0.129 |
| Stroke | 182 (2.1) | 1.35 (1.02–1.79) | 0.035 | 302 (2.0) | 1.28 (0.97–1.68) | 0.079 | 67 (1.8) | 1.15 (0.82–1.62) | 0.403 |
| New dialysis requirement | 82 (1.0) | 0.69 (0.48–1.00) | 0.053 | 193 (1.3) | 0.95 (0.68–1.33) | 0.761 | 66 (1.7) | 1.35 (0.90–2.01) | 0.145 |
| (b) |
| Outcome | Concentric Remodeling (n=8791) |
Concentric LVH (n=15,421) |
Eccentric LVH (n=3795) |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Number (%) | OR (95% CI) | p Value | Number (%) | OR (95% CI) | p Value | Number (%) | OR (95% CI) | p Value | |
| Death | 261 (3.0) | 0.97 (0.78–1.20) | 0.761 | 487 (3.2) | 0.89 (0.73–1.08) | 0.235 | 117 (3.1) | 0.78 (0.60–1.01) | 0.056 |
| PPM Requirement | 800 (10.7) | 0.84 (0.72–0.99) | 0.040 | 1476 (9.6) | 0.99 (0.85–1.15) | 0.886 | 316 (8.3) | 0.98 (0.80–1.20) | 0.853 |
| Stroke | 182 (2.1) | 1.24 (0.94–1.65) | 0.127 | 302 (2.0) | 1.17 (0.89–1.53) | 0.267 | 67 (1.8) | 1.22 (0.87–1.70) | 0.251 |
| New dialysis requirement | 82 (1.0) | 0.76 (0.52–1.12) | 0.166 | 193 (1.3) | 0.96 (0.68–1.36) | 0.825 | 66 (1.7) | 1.16 (0.77–1.76) | 0.480 |
Abbreviations: CI – confidence interval; LVH – left ventricular hypertrophy; OR – odds ratio; PPM – permanent pacemaker.
One-Year Outcomes
One-year outcomes for the overall study cohort included death (17.2%), MI (1.9%), stroke (3.8%), and new dialysis requirement (2.3%). Rates of one-year outcomes stratified by LVH pattern and severity are shown in Table S6. Unadjusted cumulative incidence curves showed statistically significant differences between LVH pattern groups for death and new dialysis requirement (Figure 2).
Figure 2.
Cumulative Incidence of One-Year Clinical Outcomes by LVH Pattern – Incidence curves for normal, concentric remodeling, concentric LVH, and eccentric LVH groups.
There were no significant associations between varying LVH patterns and one-year outcomes when compared with the normal group (Table 4b). When patients were stratified by LVH severity, only moderate concentric LVH was associated with a higher risk of new dialysis requirement when compared with the normal group (HR 1.39 95% CI 1.02–1.88) (Table S7).
Table 4.
Risk of one-year clinical outcomes by LVH pattern – (a) Unadjusted and (b) adjusted one-year clinical outcomes comparing concentric remodeling, concentric LVH, and eccentric LVH groups to the normal group (reference).
| (a) |
| Outcome | Concentric Remodeling (n=8791) |
Concentric LVH (n=15,421) |
Eccentric LVH (n=3795) |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Number (%) | OR (95% CI) | p Value | Number (%) | OR (95% CI) | p Value | Number (%) | OR (95% CI) | p Value | |
| Death | 1416 (16.1) | 0.91 (0.82–1.01) | 0.075 | 2675 (17.3) | 0.97 (0.89–1.07) | 0.552 | 727 (19.2) | 1.09 (0.97–1.21) | 0.147 |
| MI | 155 (1.8) | 0.93 (0.69–1.24) | 0.620 | 301 (2.0) | 1.02 (0.78–1.33) | 0.907 | 82 (2.2) | 1.13 (0.78–1.64) | 0.522 |
| Stroke | 338 (3.8) | 1.17 (0.95–1.43) | 0.143 | 618 (4.0) | 1.21 (1.01–1.45) | 0.044 | 125 (3.3) | 0.99 (0.78–1.27) | 0.946 |
| New dialysis requirement | 143 (1.7) | 0.76 (0.58–1.01) | 0.060 | 359 (2.3) | 1.12 (0.86–1.44) | 0.399 | 112 (3.0) | 1.43 (1.06–1.93) | 0.018 |
| (b) |
| Outcome | Concentric Remodeling (n=8791) |
Concentric LVH (n=15,421) |
Eccentric LVH (n=3795) |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Number (%) | OR (95% CI) | p Value | Number (%) | OR (95% CI) | p Value | Number (%) | OR (95% CI) | p Value | |
| Death | 1416 (16.1) | 1.03 (0.93–1.15) | 0.542 | 2675 (17.3) | 1.04 (0.95–1.15) | 0.388 | 727 (19.2) | 0.98 (0.87–1.10) | 0.747 |
| MI | 155 (1.8) | 1.05 (0.76–1.46) | 0.757 | 301 (2.0) | 1.12 (0.82–1.52) | 0.477 | 82 (2.2) | 1.07 (0.71–1.63) | 0.737 |
| Stroke | 338 (3.8) | 1.11 (0.89–1.39) | 0.362 | 618 (4.0) | 1.14 (0.92–1.40) | 0.224 | 125 (3.3) | 1.01 (0.78–1.32) | 0.919 |
| New dialysis requirement | 143 (1.7) | 0.86 (0.64–1.15) | 0.314 | 359 (2.3) | 1.17 (0.91–1.52) | 0.230 | 112 (3.0) | 1.25 (0.92–1.70) | 0.159 |
Abbreviations: CI – confidence interval; HR – hazard ratio; LVH – left ventricular hypertrophy; MI – myocardial infarction.
DISCUSSION
This analysis of a large cohort of real-world patients who underwent TAVR revealed the following findings: 1) approximately 60% of patients had some degree of LVH, and most of these had a concentric pattern. 2) The pattern and severity of LVH varied by sex. 3) There were no significant associations between varying LVH patterns or severity and clinical outcomes during index hospitalization and at one-year follow-up. Thus, this analysis suggests that the pattern and severity of pre-procedure LVH, as determined by sex-specific cutoffs for LVMI and RWT, is not associated with clinical outcomes up to one-year after TAVR. These findings differ from patients with hypertension, where LVH is associated with a hazard ratio of approximately 1.6 – 4.0 for fatal and non-fatal cardiovascular events (21).
The primary findings in the current study contrast with older reports of patients undergoing SAVR, which showed higher odds of in-hospital mortality (ranging from 2.1 – 38.0) in patients with LVH compared with those without LVH (12)(13)(14). In a more contemporary cohort of patients, Minamino-Muta and colleagues demonstrated that in Japanese patients with severe AS who underwent SAVR or TAVR, outcomes did not differ between patients with high LVMI versus normal LVMI pre-operatively (15). The present analysis corroborates this finding in a larger cohort of patients who underwent TAVR exclusively. The change in outcomes of patients with LVH prior to SAVR may reflect improvement in cardiac anesthesia, surgical technique, and post-operative care over time. Additionally, the surgical risk of patients undergoing SAVR has decreased, partially due to the introduction of TAVR (22)(23).
There are several potential reasons why pre-procedure LVH was not associated with adverse clinical outcomes in patients undergoing TAVR. The development of LVH is likely somewhat adaptive in most patients with severe AS and allows for myocardial compensation in the setting of progressive LV hemodynamic loading. If severe aortic stenosis is the primary stimulus for LVH, then TAVR should facilitate reverse remodeling of the LV and a subsequent reduction in LVMI. Furthermore, an increased rapidity and extent of reverse remodeling after TAVR is associated with improved clinical outcomes (24)(25). Thus, a higher pre-procedure LVMI may be a proxy for greater reverse remodeling after TAVR. Additionally, most adverse outcomes soon after TAVR are non-cardiac in nature (e.g. pneumonia, bleeding) (26). Consequently, some intrinsic cardiac factors, such as LVH, may not play a substantial role in patients’ post-TAVR clinical trajectory.
Together, these findings suggest that TAVR is safe and likely to benefit patients with severe AS regardless of pre-procedure LVH severity or pattern up to one-year. Further studies are needed to elucidate how LVH impacts longer-term outcomes after TAVR, particularly as studies evaluating TAVR in low-risk populations are ongoing.
Study Limitations
Our study should be interpreted in the context of several limitations. First, despite the numerous variables tabulated in the TVT Registry, certain factors were not included for adjustment in the multivariable models. For example, LV diastolic dysfunction was recently shown to be associated with increased risk of all-cause mortality after TAVR (27). Additionally, the severity of LV intracavitary flow gradient has been associated with adverse outcomes in SAVR, as well as in case reports of TAVR patients (28)(29). However, both LV diastolic dysfunction and intracavitary flow gradient are not captured in the TVT Registry. Additionally, the database does not include follow-up echocardiographic data regarding LV mass regression after TAVR, which has been associated with improved outcomes (24)(25). Second, the degree of myocardial fibrosis for each patient was not able to be adjusted for, and this may confound the outcomes observed. Third, though the analysis was adjusted for common mechanical (AS, hypertension) and non-mechanical (anemia, end-stage renal disease) causes of LVH, rates of additional causes of LVH (e.g. amyloidosis, thyroid disease, cocaine use) were unknown for each study group. Fourth, the association between LVH and longer-term (beyond one-year) outcomes after TAVR may differ and were not evaluated in the current study. Fifth, echocardiographic parameters are site-reported in the TVT Registry and are not adjudicated by a central core laboratory. Thus, there may have been some interpretation variability in echocardiographic measurements of wall dimensions. Sixth, given the observational nature of this study, there may be additional unmeasured confounders that could not be accounted for in the regression models. Lastly, because one-year outcomes were derived from administrative claims data, it is possible that some outcomes were misclassified due to miscoding.
Conclusions
Among patients undergoing commercial TAVR in the United States, pre-procedure LVH pattern or severity, according to sex-specific cutoffs for LVMI and RWT, did not modify the risk of death, MI, stroke, or new dialysis requirement at one-year follow-up. Further studies are needed to compare outcomes between patients with LVH who undergo TAVR accounting for LV diastolic dysfunction, intracavitary flow gradient, LVMI regression, and myocardial fibrosis and to determine the longer-term impact of pre-procedure LVH on TAVR outcomes.
Supplementary Material
What’s known? LVH is an independent predictor of adverse clinical outcomes in patients with aortic stenosis. The impact of LVH prior to TAVR has not been extensively studied.
What’s new? The TVT Registry was used to examine in-hospital and 1-year clinical outcomes after TAVR in 31,199 patients with varying LVH pattern and severity, according to sex-specific cutoffs for LVMI and RWT. Pre-procedure LVH pattern or severity did not meaningfully impact the risk of adverse clinical outcomes.
What’s next? Further studies are needed to compare outcomes between patients with LVH who undergo TAVR accounting for LV diastolic dysfunction, intracavitary flow gradient, LVMI regression, and myocardial fibrosis and to determine the impact of pre-procedure LVH on TAVR outcomes beyond 1-year.
Funding:
This research was supported by the American College of Cardiology Foundation’s National Cardiovascular Data Registry and the Society of Thoracic Surgeons.
Sreekanth Vemulapalli: Research Grants: American College of Cardiology, Society of Thoracic Surgeons, Patient Centered Outcomes Research Institute, Boston Scientific, Abbott Vascular. Consulting / Speakers Bureau: Boston Scientific, Janssen, Premiere, Pfizer.
Ajay J. Kirtane: Institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical; Personal: Conference honoraria and Travel/Meal reimbursements only.
Binita Shah: Research Grants: VA Office of Research and Development (iK2CX001074) and Siemens Medical Solutions. Advisory Board: Philips Volcano.
Angela Lowenstern: Research Grants: NIH T-32 training grant #5 T32 HL069749–14.
Andrzej Kosinski: Research Grants: American College of Cardiology, American Heart Association, Society of Thoracic Surgeons, Patient Centered Outcomes Research Institute.
Deepak L. Bhatt: Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, PLx Pharma, Takeda.
Abbreviations
- ACC
American College of Cardiology
- AS
aortic stenosis
- CPB
cardiopulmonary bypass
- LVH
left ventricular hypertrophy
- LVM
left ventricular mass
- LVMI
left ventricular mass index
- RWT
relative wall thickness
- SAVR
surgical aortic valve replacement
- STS
Society for Thoracic Surgeons
- TAVR
transcatheter aortic valve replacement
- TVT
Transcatheter Valve Therapies
Footnotes
Disclosures:
Anubodh Varshney: None.
Pratik Manandhar: None.
Verghese Mathew: None.
Tsuyoshi Kaneko: speakers bureau for Edwards, Medtronic and Abbott.
Vinod H. Thourani: none
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