Five-Year Transcatheter Aortic Valve Replacement Outcomes in Chronic Hemodialysis vs. Non-Hemodialysis Patients Using Balloon-Expandable Devices

Abstract

Background: Based on the results of a clinical trial in Japan, transcatheter aortic valve replacement (TAVR) for hemodialysis (HD) patients gained approval; however, mid-term TAVR outcomes and transcatheter aortic valve (TAV) durability in HD patients remain unexplored.

Methods and Results: We analyzed background, procedural, in-hospital outcome, and follow-up data for 101 HD patients and 494 non-HD patients who underwent TAVR using balloon-expandable valves (SAPIEN XT or SAPIEN 3) retrieved from Osaka University Hospital TAVR database. Periprocedural mortality and TAVR-related complications were comparable between HD and non-HD patients. However, Kaplan-Meier analysis revealed that HD patients had significantly lower survival rates (log-rank test, P<0.001). In addition, HD patients had significantly higher rates of severe structural valve deterioration (SVD) than non-HD patients (Gray test, P=0.038).

Conclusions: TAVR in HD patients had comparable periprocedural mortality but inferior mid-term survival and TAV durability than in non-HD patients. Indications for TAVR in younger HD patients should be carefully determined, considering the possibility of a TAV-in-TAV procedure when early SVD occurs.

Transcatheter aortic valve replacement (TAVR) has established its non-inferiority to surgical aortic valve replacement (SAVR) in low-risk patients with severe aortic stenosis (AS), and its indications are expanding to younger, lower surgical risk individuals worldwide.^1,2 With advancing technology, the focus of concern has shifted from periprocedural complications to lifelong AS management through TAVR. From this perspective, structural valve deterioration (SVD) remains a major issue in TAVR, especially among younger patients.^3,4 Although the TAV-in-TAV procedure holds promise, its feasibility is limited due to anatomical constraints.⁵ Moreover, it remains uncertain whether a second TAV is more durable than the first. To broaden the indications for TAVR and provide lifelong management for younger patients, investigating the duration and mechanism of SVD is crucial. In Japan, TAVR indications were expanded to include hemodialysis (HD) patients in 2021. However, the long-term effectiveness of TAVR in managing the lives of HD patients remains unexplored. The aim of this study was to investigate the mid-term outcomes of TAVR, including severe SVD, in Japanese HD patients treated for AS with the SAPIEN XT (XT) or SAPIEN 3 (S3) compared with non-HD patients.

Methods

Patient Selection

This retrospective single-center observational study included patients with severe AS who underwent TAVR using XT or S3 at Osaka University Hospital between May 2010 and April 2022. As shown in Figure 1, patients treated with the first-generation balloon-expandable SAPIEN (Edwards Lifesciences) or other TAV devices, those who underwent non-native aortic valve (TAV-in-TAV and TAV-in-surgical bioprosthetic aortic valve) procedure, and patients with bicuspid aortic valves were excluded. In addition, the patients without available preprocedural multislice electrocardiogram-gated computed tomography (MSCT) or transthoracic echocardiographic data at baseline and within 3 months after TAVR were excluded from the study. Patients undergoing HD were compared to those not receiving HD.

Figure 1.

Patient selection for the study. CT, computed tomography; HD, hemodialysis; TAVR, transcatheter aortic valve replacement.

The study was approved by the Institutional research ethics committee of Osaka University Hospital, and adhered to the tenets of the Declaration of Helsinki. The requirement for informed consent was waived.

TAVR Procedure and Follow-up

For all patients, the indication for TAVR was decided by the Osaka University Hospital heart team in accordance with Japanese guidelines.^6,7 In addition, preprocedural valve sizing and determination of the TAVR access site were done using preprocedural MSCT analysis with 3 mensio Structural Heart ver. 8.1 (Pie Medical Imaging, Bilthoven, Netherlands). TAVR was conducted under general anesthesia, with the choice of either transesophageal echocardiography guidance or local sedation with transthoracic echocardiography (TTE). After discharge, TTE follow-up was done at 1 or 3 months, 6 months, and 1 year, and thereafter annually in the outpatient clinic of Osaka University Hospital.

Study Outcomes

We compared periprocedural and early mortality between HD and non-HD patients. Furthermore, we assessed mid-term TAVR outcomes, encompassing not only survival rates but also the incidence of severe SVD, in both patient groups. In this study, we defined periprocedural mortality and early mortality in accordance with the Valve Academic Research Consortium 3 (VARC3) definitions.⁸ “Severe SVD” was defined as SVD causing severe hemodynamic valve deterioration (Stage 3 severe hemodynamic valve deterioration according to VARC3 criteria) and counted as an event of SVD.

Statistical Analysis

We compared baseline patient characteristics, including TTE parameters and MSCT measurements, between HD and non-HD patients. Data are expressed as numbers and percentages, mean±SD, or the median with interquartile range (IQR). Continuous variables were compared between groups using an unpaired t-test or the Mann-Whitney U test, depending on data distribution. Categorical variables were compared using the Chi-squared test or Fisher’s exact test, as appropriate. The Kaplan-Meier method was used to estimate the survival rate after the procedure, with survival curves for HD and non-HD patients compared using the log-rank test. We performed Cox proportional hazard models for all-cause mortality in HD patients, with the following clinical characteristics included in the model: sex, age, New York Heart Association (NYHA) class, previous history of myocardial infarction (MI), left ventricular ejection fraction (LVEF) as determined by TTE, albumin, and comorbidities (hypertension, diabetes, dyslipidemia). The incidence of severe SVD was calculated, and HD and non-HD patients were compared using the cumulative incidence method to consider death before the onset of SVD as a competing risk, tested using the Gray test. Finally, to adjust the follow-up period, the incidence rate of severe SVD per 100 person-years for HD and non-HD patients was calculated, and the incidence rate ratio was estimated through Poisson regression.

Statistical analyses were performed using R version 4.2.2 (R Foundation for Statistical Computing, Vienna, Austria; http://www.r-project.org/).

Results

In all, 595 who underwent TAVR with XT or S3 were included in this study (101 patients receiving HD, 494 patients not receiving HD). HD patients were younger, predominantly male, and had a lower prevalence of classical atherosclerotic risk factors, such as hypertension and dyslipidemia, compared with the non-HD patients. Conversely, a history of cardiac surgery and the presence of peripheral artery disease were significantly more common in HD patients, resulting in a statistically higher Society of Thoracic Surgeons risk score. With regard to laboratory data, serum albumin concentrations were significantly lower in HD than non-HD patients (Table 1). In preprocedural TTE assessments, although baseline AS severity was similar between the HD and non-HD groups, LVEF was significantly lower in HD than non-HD patients before (Table 2) and after (Table 3) the TAVR procedure. In the preprocedural MSCT analysis of the aortic valve complex, HD patients had significantly larger anatomies than non-HD patients, although there were no significant differences in the amount of calcification calculated using the 3 mensio software (Table 2).

Table 1.

Baseline Characteristics in HD and Non-HD Patients

	HD patients (n=101)	Non-HD patients (n=494)	P value
Age (years)	79.30±6.83	83.64±5.65	<0.0001
Male sex	63 (62.4)	168 (34.0)	<0.0001
BSA (m2)	1.49±0.17	1.44±0.17	0.006
NYHA Class III or IV	43 (42.6)	206 (41.7)	0.959
Previous stroke	24 (23.8)	75 (15.2)	0.04
Previous cardiac surgery	21 (20.8)	46 (9.3)	0.001
Previous MI	12 (11.9)	46 (9.3)	0.461
Previous PCI	28 (27.7)	111 (22.5)	0.25
Previous PMI	5 (5.0)	33 (6.7)	0.66
Hypertension	73 (72.3)	406 (82.2)	0.031
Diabetes	39 (38.6)	184 (37.2)	0.884
Dyslipidemia	46 (45.5)	305 (61.7)	0.004
COPD	17 (16.8)	87 (17.6)	0.965
PAD	43 (42.6)	135 (27.3)	0.003
AF	22 (21.8)	106 (21.5)	1.00
Laboratory data
Hemoglobin (g/dL)	11.30±0.16	11.42±0.07	0.507
Albumin (g/dL)	3.54±0.04	3.71±0.02	0.0005
Duration of HD (years)	9.04±8.10
STS score (%)	11.60 [8.65–17.28]	6.50 [4.68–9.80]	<0.0001

Unless indicated otherwise, data are presented as the mean±SD, n (%), or median [interquartile range]. AF, atrial fibrillation; BSA, body surface area; COPD, chronic obstructive pulmonary disease; HD, hemodialysis; MI, myocardial infarction; NYHA, New York Heart Association; PAD, peripheral artery disease; PCI, percutaneous coronary intervention; PMI, pacemaker implantation; STS, Society of Thoracic Surgeons.

Table 2.

TTE and MSCT Parameters Before the Transcatheter Aortic Valve Replacement Procedure

	HD patients (n=101)	Non-HD patients (n=494)	P value
TTE assessment
Peak velocity (m/s)	4.14±0.64	4.30±0.67	0.029
Mean PG (mmHg)	43.09±13.56	45.99±15.32	0.078
AVA (cm2)	0.72±0.16	0.71±0.16	0.769
LVEF (%)	53.95±13.70	63.65±13.10	<0.001
MSCT assessment
Area-derived annulus diameter (mm)	23.83±1.89	22.84±2.06	<0.001
Valsalva sinus (mm)
LCC	31.49±3.24	29.93±3.37	<0.001
RCC	31.04±3.11	29.42±3.25	<0.001
NCC	31.89±3.00	30.46±3.24	<0.001
Amount of calcification (mm3)	386.00 [214.40–552.40]	356.60 [205.60–595.00]	0.824
LCA height (mm)	13.35±2.57	12.87±2.46	0.075
RCA height (mm)	17.42±2.76	15.96±2.79	<0.001
Mean STJ diameter (mm)	27.37±3.02	26.00±3.08	<0.001
Ascending aorta (mm)	33.04±3.10	32.62±3.56	0.265

Unless indicated otherwise, data are presented as the mean±SD or median [interquartile range]. AVA, aortic valve area; HD, hemodialysis; LCA, left coronary artery; LCC, left coronary cusp; LVEF, left ventricular ejection fraction; MSCT, multislice electrocardiogram-gated computed tomography; NCC, non-coronary cusp; PG, pressure gradient; RCA, right coronary artery; RCC, right coronary cusp; STJ, sinotubular junction; TTE, transthoracic echocardiography.

Table 3.

TAVR Procedure and Outcomes

	HD patients (n=101)	Non-HD patients (n=494)	P value
TAVR procedure
Transfemoral approach	72 (71.3)	342 (69.2)	0.771
Device
SAPIEN XT	19 (18.8)	200 (40.5)	<0.001
SAPIEN 3	82 (81.2)	294 (59.5)
TAV size
20 mm	1 (1.0)	29 (5.9)	0.001
23 mm	40 (39.6)	274 (55.5)
26 mm	47 (46.5)	157 (31.8)
29 mm	13 (12.9)	34 (6.9)
Annulus rupture	2 (2.0)	3 (0.6)	0.436
New PMI	8 (7.9)	36 (7.3)	0.99
Periprocedural mortality	2 (2.0)	11 (2.2)	1.000
Early mortality	17 (16.8)	34 (6.9)	0.003
TTE assessment after TAVR
Peak velocity	2.18±0.04	2.16±0.02	0.580
Mean PG	10.69±3.98	10.26±4.03	0.335
EOA	1.72±0.42	1.73±0.42	0.736
EOAi	1.16±0.28	1.21±0.29	0.082
PPM ≥moderate	9 (8.9)	34 (6.9)	0.613
PVL ≥moderate	1 (1.0)	13 (2.6)	0.528
LVEF	57.37±13.69	65.53±11.48	<0.001

Unless indicated otherwise, data are presented as the mean±SD or n (%). EOA, effective orifice area; EOAi, effective orifice area index; HD, hemodialysis; LVEF, left ventricular ejection fraction; PG, pressure gradient; PMI, pacemaker implantation; PPM, prosthesis-patient mismatch; PVL, paravalvular leakage; TAV, transcatheter aortic valve; TAVR, transcatheter aortic valve replacement; TTE, transthoracic echocardiography.

The TAVR procedure was successfully completed in all patients. The transfemoral approach was comparable in both groups; however, after introducing the S3 delivery system and expandable sheath, the transfemoral approach increased significantly in non-HD patients (data not shown), reflecting a lower prevalence of peripheral artery disease in this group. Regarding the label size of the implanted TAVs, HD patients received larger valves, in line with their larger annulus diameter. Periprocedural mortality and complications (e.g., annulus rupture and implanted valve function assessed using TTE) were similar in the 2 groups (Table 3). Consequently, periprocedural mortality was comparable between HD and non-HD patients (2.0% vs. 2.2%, respectively; Table 3). However, early mortality was significantly higher in HD than non-HD patients (16.8% vs. 6.9% respectively; P<0.003; Table 3). In the survival analysis, the survival rate was lower for HD than non-HD patients (median 24.7% [IQR 15.9–38.4%] vs. 54.4% [IQR 49.1–60.2%] at 5 years; log-rank test, P<0.001; Figure 2A). Moreover, this result did not change when survival in HD and non-HD patients was evaluated according to the type of balloon-expandable valve, with median survival at 5 years being 26.3% (IQR 12.4–55.8%) and 55.7% (IQR 49.1–63.2%) for the XT group and 25.1% (IQR 14.9–42.2%) and 49.0% (IQR 45.3–64.6%) for the S3 group (log-rank test, P<0.001; Figure 2B). The Cox proportional hazard models revealed that NYHA class, LVEF at baseline, and serum albumin concentrations were predictive factors for all-cause mortality in HD patients (Table 4).

Figure 2.

(A) Kaplan-Meier survival curves after transcatheter aortic valve replacement (TAVR) for hemodialysis (HD) and non-HD patients. (B) Kaplan-Meier survival curves for HD and non-HD patients divided by each valve, SAPIEN XT (XT) and SAPIEN3 (S3).

Table 4.

Multivariable Baseline Predictors for All-Cause Mortality in Hemodialysis Patients

	HR (95% CI)	P value
Age	1.00 (0.95–1.05)	0.919
Male sex	1.29 (0.72–2.32)	0.398
NYHA class	2.11 (1.32–3.39)	0.002
Previous MI	0.77 (0.31–1.92)	0.574
Hypertension	0.71 (0.40–1.26)	0.241
Diabetes	1.72 (0.98–3.02)	0.058
Dyslipidemia	0.69 (0.36–1.30)	0.247
LVEF at baseline	0.98 (0.96–1.00)	0.037
Albumin at baseline	0.44 (0.20–0.95)	0.037

CI, confidence interval; HR, hazard ratio; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NYHA, New York Heart Association.

During the follow-up period, severe SVD, in the form of Stage 3 severe hemodynamic valve deterioration, was observed in 12 patients. Of these patients, 4 were undergoing HD, whereas the remaining 8 were not on HD. The mean duration from the initial TAVR to the diagnosis of severe SVD was 3.32±1.52 years in the HD patients and 5.74±2.17 years in the non-HD patients. The diagnosis of severe SVD was made during annual follow-up TTE in 11 patients, with 1 patient diagnosed via a combination of TTE and MSCT (Figure 3C) due to transfer to Osaka University Hospital for acute decompensated heart failure with reduced LVEF.

Figure 3.

Representative multislice electrocardiogram-gated computed tomography (MSCT) images after transcatheter aortic valve replacement with the SAPIEN 3 (S3). The black dashed lines show the stent frame of the implanted S3. White arrows indicate calcification of the native aortic valve pushed away by the S3 stent frame. Blue arrows indicate non-calcified normal bovine pericardial leaflets of the S3. Red arrows indicate calcified bovine pericardial tissue of the S3. (A) Normal MSCT image of bovine pericardium leaflets of S3. (B,C) Typical MSCT images of calcified bovine pericardium leaflets causing severe structural valve deterioration in hemodialysis patients.

Similarly, the cumulative incidence of severe SVD was significantly higher among HD than non-HD patients when considering competing risks (median 4.61% [IQR 2.96–6.26%] vs. 1.11% [IQR 0.99–1.23%] at 5 years; Gray’s test, P=0.038; Figure 4A). Even when the cumulative incidence of severe SVD was analyzed for the XT and S3 valves separately, there was a trend for higher rates of severe SVD among HD than non-HD patients (median 10.5% [IQR 3.25–17.7%] vs. 1.60% [IQR 1.41–1.79%] at 5 years for XT [Gray test, P=0.095]; median 1.74% [IQR 0.34–3.14%] vs. 0% at 5 years for S3 [Gray test, P=0.042]; Figure 4B). The incidence rates of severe SVD per 100 person-years in the HD and non-HD groups were 1.81 and 0.49 events, respectively, with an incidence rate ratio of 3.66 (95% confidence interval 1.10–12.2; P=0.034).

Figure 4.

(A) Cumulative incidence of severe structural valve deterioration (SVD) in hemodialysis (HD) and non-HD patients using the Gray test. (B) Cumulative incidence of severe SVD in HD and non-HD patients divided by each valve, SAPIEN XT (XT) and SAPIEN3 (S3).

The type of severe SVD was recurrent calcified severe AS in 11 patients and a combination of moderate transvalvular aortic regurgitation (AR) and calcified moderate AS in 1 patient. As shown in Figure 3B,C, thin superficial calcifications on the leaflets of the TAVs (red arrows) were characteristic of AS recurrence, as assessed by MSCT. Among the 12 patients with severe SVD, 10 were successfully treated with TAV-in-TAV or SAVR, whereas the other 2 patients were left untreated due to severe dementia and advanced age.

Discussion

The present study is the first to investigate and compare the mid-term outcomes of TAVR using XT or S3 in both HD and non-HD patients. The major findings of this study are as follows: (1) the survival rate after TAVR was significantly lower among HD than non-HD patients despite similar periprocedural mortality in both groups; (2) the incidence of severe SVD at 5 years after TAVR was significantly higher among HD than non-HD patients, a trend consistent across all analyses; and (3) the predominant pathophysiology of severe SVD in the XT and S3 appeared to be the recurrence of AS, primarily caused by calcium accumulation on the bovine pericardium leaflets rather than transvalvular AR due to leaflet tearing or prolapse.

Early to Mid-Term Survival Rate After TAVR in HD Patients

The estimated survival of HD patients following SAVR is approximately 40% at 5 years.^9,10 Because the perioperative mortality rate in HD patients after SAVR is also as high as 10–20%, poor mid-term prognosis following SAVR is considered to be partly due to the invasive nature of cardiac surgery. In the present study, although TAVR reduced perioperative mortality in HD patients, this improvement did not directly translate to better mid-term prognosis after TAVR, despite a clinical trial in Japan using S3 demonstrating comparable early mortality rates for TAVR in HD patients.¹¹ In the present study, we found that NYHA class, preprocedural LVEF determined by TTE, and serum albumin concentration were predictive factors for all-cause mortality after TAVR in HD patients. A low serum albumin concentration has been reported as an independent factor for all-cause mortality after TAVR in previous studies.^12,13 However, whether the albumin concentration itself directly contributes to mortality after TAVR or it is simply a surrogate marker remains unclear. In contrast, regarding LVEF and NYHA class, there is room for intervention. Given the rapid progression of AS in HD patients, it is critical to diagnose AS in its early stages before LVEF begins to decline after the peak severity of AS is over. Moreover, it may be important to intervene at a moderate-to-severe stage of AS to improve the prognosis of HD patients; however, further research is essential to confirm this.

Incidence of SVD in TAVs

In case of TAVs, the incidence of SVD has been reported using various definitions. In 2018, using the 2017 European Association of Percutaneous Cardiovascular Interventions (EAPCI)/European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) definition, the incidence of SVD for the first-generation balloon-expandable valves (SAPIEN) was approximately 10–20% at 7 years.³ This may not be surprising because TAVs have certain disadvantages compared to SAVs. First, TAVs must be compressed in the delivery catheter, which may damage the leaflet material, potentially impacting durability.¹⁴ Second, the inability to remove native aortic valve tissues could increase stress on TAV leaflet material, accelerating degeneration.

In 2020, using VARC3 criteria, Pibarot et al reported that the incidence of severe SVD at 5 years was 0.8% with SAVs, 3.7% with second-generation XT, and 1.1% with third-generation S3 according to Kaplan-Meier analysis.¹⁵ In the present study, the rate of severe SVD in non-HD patients after 5 years of follow-up was 0% with S3 and 2.5% with XT according to Kaplan-Meier analysis. Given the improvement in the durability of the latest anticalcification treatment technology, it is expected that the durability of TAVs will be further enhanced in the fourth-generation balloon-expandable SAPIEN 3 Ultra RESILIA (Edwards Lifesciences).^16,17

The durability of TAVs in HD patients remains unknown due to their exclusion from randomized controlled trials. Furthermore, the markedly poorer prognosis of HD patients hampers the accurate determination of the true incidence of severe SVD. In the present study, the Gray test was used to estimate the incidence of severe SVD in XT and S3 in HD patients, and we found that HD patients had a higher incidence of severe SVD than non-HD patients. In addition, when we compared the incidence rates of severe SVDs using the exposure-adjusted method, the incidence was 1.81% per 100 patient-years in HD patients, compared with 0.49% per 100 patient-years in non-HD patients. The mean time to severe SVD in HD patients was approximately half that in non-HD patients. Our results imply that HD patients exhibit more than double the rate of progression of TAV stenosis due to calcium accumulation than non-HD patients.¹⁸ Therefore, the indication for TAVR in younger HD patients should be considered cautiously, unless TAV-in-TAV procedures are anatomically feasible.

Related Technological and Technical Factors for SVD

This study also demonstrated that the durability of TAV tended to be better for S3 than XT. To understand the improved durability of S3, the technological and technical advancements adopted in the S3 should be noted. The major differences between XT and S3 are the addition of a sealing cuff and a longer stent frame height. In the present study, the presence of paravalvular leakage greater than mild after TAVR was significantly lower in the S3 than XT group, indicating that the sealing cuff of the S3 was functioning effectively. The longer stent frame height made it easier to visualize the radiolucent line of the crimped S3 when implanting. It allowed for more accurate positioning of the S3 at the native annular position, similar to SAVR. The correct annular positioning of S3 reduced the rate of new pacemaker implantation in our study (10.1% for XT and 5.9% for S3; P=0.07); however, these improvements did not directly correlate with better durability. The longer stent frame height and higher implantation of S3 both contributed to elevating the position of leaflet coaptation. This may potentially have a role in reducing the residual pressure gradient after TAVR, which may have improved durability. Thus, TAVs with higher leaflet coaptation may be an ideal choice for extending their durability.

SVD can be classified into 2 types according to the functional abnormality: AS recurrence due to leaflet calcification and transvalvular AR due to leaflet tear or prolapse. It has been reported in SAVs that bovine pericardial tissue tends to develop AS due to calcification, whereas porcine tissue tends to develop AR due to leaflet tears or prolapse.¹⁹ The different SVD phenotypes are explained by differences in tissue thickness and anticalcification treatment. In the present study, the main cause of severe SVD was the calcification of the bovine pericardial tissue leaflets of TAVs. As shown in Figure 3B,C, unlike native aortic valve calcification (Figure 3, white arrows), superficially thin but diffuse calcification (Figure 3B,C, red arrows) can cause severe AS in bovine pericardial tissue leaflets. Therefore, further advances in anticalcification treatments are essential for prolonging the durability of bovine pericardial tissue valves.

Patient Background Factors Associated With SVD

There are numerous and complex contributors to bioprosthetic valve degeneration. Among these factors, chronic HD is the most well-known contributor to accelerated bioprosthetic valve calcification, due primarily to impaired calcium and phosphate metabolism. HD causes secondary hyperparathyroidism, which activates bone remodeling, resulting in ectopic calcium phosphate accumulation on the bioprosthetic valve leaflets.²⁰

Other factors associated with SVD include younger age, female sex, small annulus, prosthesis-patient mismatch (PPM) and diabetes.^15,19,21 In the present study, the mean age of patients with severe SVD was significantly lower (74.8±1.7 vs. 83.1±5.9 years; P<0.001), and they tended to be female (83.3% vs. 60.7%; P=0.111) with smaller annuli (21.8±1.9 mm vs. 23.0±2.1 mm; P=0.044). However, there was no significant difference in the rate of diabetes (33.3% vs. 37.6%; P=1.000) or the value of the indexed effective orifice area (EOAi) as an indicator for PPM (1.13±0.28 vs. 1.20±0.29, P=0.377) between patients with and without severe SVD. Two potential mechanisms for SVD in females have been discussed previously.²² First, women generally have smaller body sizes and smaller annuli, leading to severe PPM and a higher residual pressure gradient. This increased stress on the implanted valve tissue can result in earlier valve degeneration. Second, postmenopausal women are more prone to osteoporosis, which accelerates the calcification of bioprosthetic valve leaflets. All female patients with severe SVD had small annuli and were implanted with 20- or 23-mm TAVs in our study; however, none of them exhibited severe PPM after TAVR and there was no significant difference in the rate of PPM (EOAi <0.85) after TAVR between SVD and non-SVD patients.

Based on these results, it is crucial to carefully consider the suitability of TAVR for patients with risk factors for SVD, such as age <75 years, on HD, or female with small annuli. Further studies and data accumulation are necessary to fully understand the risk factors and complex mechanisms underlying SVD.

Study Limitations

This study has several limitations. First, it was a non-randomized observational study. Second, the sample size was relatively small, and the follow-up period, especially for HD patients, was limited. Third, there is potential selection bias, particularly among non-HD patients. For example, we tended to prefer self-expandable devices for non-HD patients with bulky calcification to minimize the risk of annulus rupture and for those with small annuli to reduce the remaining pressure gradient. In contrast, we had no choice but to use balloon-expandable valves for HD patients. These selection factors may have possibly influenced the durability of each type of TAV.

Conclusions

TAVR in HD patients exhibits comparable periprocedural mortality but inferior mid-term survival and TAV durability compared with non-HD patients. Indications for TAVR in younger HD patients should be carefully determined, considering the possibility of TAV in TAV when early SVD occurs.

Acknowledgment

The authors thank all the members of the Osaka University Hospital heart team who contributed to the data acquisition and cooperated with the TAVR procedure.

Sources of Funding

This study did not receive any specific funding.

Disclosures

I.M. has received scholarship funds from Abbott Medical Japan and Medtronic Japan. Y.S. is a member of Circulation Journal’s Editorial Team.

IRB Information

This study was approved by the Institutional research ethics committee of Osaka University Hospital (Approval no. 23310).

Data Availability

Our study data will not be made available to other researchers for purposes of reproducing the results because of Institutional Review Board restrictions.

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