Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement on Changes in Cardiac Sympathetic Nervous Function: Assessment by 123I-Metaiodobenzylguanidine Myocardial Scintigraphy

概要

Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve
Replacement on Changes in Cardiac Sympathetic Nervous Function:
Assessment by 123I-Metaiodobenzylguanidine Myocardial Scintigraphy

Kazuhiro Nitta,1 MD, Yukihiro Fukuda,1 MD, Hitoshi Susawa,1 MD, Hiroki
Ikenaga,1 MD, Hiroto Utsunomiya,1 MD, Ken Ishibashi,1 MD, Satoshi
Kurisu,1 MD, Shinya Takahashi,2 MD, Yukiko Nakano,1 MD, Kazuo Awai,3
MD, Taijiro Sueda,2 MD and Yasuki Kihara,1 MD

1Department

of Cardiovascular Medicine, Hiroshima University Graduate

School of Biomedical and Health Sciences, Hiroshima, Japan
2Department

of Cardiovascular Surgery, Hiroshima University Graduate

School of Biomedical and Health Sciences, Hiroshima, Japan
3Department

of Diagnostic Radiology, Hiroshima University Graduate School

of Biomedical and Health Sciences, Hiroshima, Japan

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Introduction
Aortic stenosis (AS) is a cardiovascular disease which is common among
elderly patients. Transcatheter aortic valve replacement (TAVR) has recently
emerged as a minimally invasive therapeutic option. However, prosthesispatient mismatch (PPM)—which occurs when the effective orifice area of the
implanted prosthetic valve is too small in relation to the patient’s body surface
area—is an important potential complication of TAVR. Several studies have
shown PPM to be associated with increased mortality after TAVR. 123Imetaiodobenzylguanidine (MIBG) myocardial scintigraphy has been widely
used for the assessment of CSN activity and represents a useful prognostic
marker in patients with heart failure. However, the impact of PPM after
TAVR on changes in CSN function remains unclear. The present study aimed
to investigate the impact of PPM after TAVR on CSN activity using 123IMIBG scintigraphy.

Methods
Study Population
We recruited a total of 117 patients with symptomatic severe AS who

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underwent TAVR between February 2016 and May 2019 at the Hiroshima
University Hospital. Severe AS was defined as an aortic valve area (AVA) of
<1.0 cm2 and a resting or inducible peak transaortic velocity >4 m/s or mean
pressure gradient of ≥40 mmHg. Of these, 58 underwent 123I-MIBG
scintigraphy at baseline and at about 9 months after TAVR. Exclusion criteria
were as follows: (1) prior cardiac surgery (n = 2), (2) presence of unstable preprocedural conditions (n = 2), (3) undergoing TAVR with the trans-apical or
trans-aortic approach (n = 3), and (4) permanent pacemaker implantation (n
= 6) or hemodialysis (n = 1) after TAVR. Finally, 44 patients were enrolled in
this study.

Transcatheter Aortic Valve Replacement
The procedure was performed using either a balloon-expandable Edwards
Sapien XT/Sapien 3 or self-expandable Medtronic CoreValve Evolut R device.
All patients were treated using a transfemoral approach under general
anesthesia.

123I-Metaiodobenzylguanidine Scintigraphy

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123I-MIBG was administered intravenously at a dose of 111 MBq. Anterior
planar images were obtained at 15 min (early image) and 210 min (delayed
image) after injection using a dual-detector 90° γ-camera with a mediumenergy general collimator. Images were analyzed based on the region of
interest determined using dedicated software (Jetpack, Hitachi) by an
experienced radiology technician who was blinded to the clinical status of
the patients. The Jetpack software was able to semi-automatically
determine heart-to-mediastinum (H/M) ratios and correct them to standard
medium-energy collimator conditions. Early and delayed H/M ratios were
calculated by measuring the average counts in each region. The washout
rate (WR) was calculated by: [(H−M) early − (H−M) delayed/k] × 100/(H−M)
early, with background subtraction and time-decay correction (k = timedecay coefficient). Changes between pre- and post-procedural 123I-MIBG
parameters were calculated using the following formulae: (1) ΔH/M ratio =
(post-procedural H/M ratio) − (baseline H/M ratio) and (2) ΔWR = (baseline
WR) − (post-procedural WR).

Transthoracic Echocardiography

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We obtained echocardiographic data at baseline and at 7 days and 9 months
after TAVR. Comprehensive echocardiographic assessments were performed
by three experienced sonographers, who had no knowledge of the patients’
clinical statuses. The severity of PPM was classified using an indexed
effective orifice area, with moderate defined as >0.65 and ≤0.85 cm2/m2 and
severe defined as <0.65 cm2/m2, and this was assessed by echocardiogram at
7 days after TAVR.

Results
Patient Characteristics Before Transcatheter Aortic Valve Replacement in
Relation to Patient-Prosthesis Mismatch
There were 9 male and 35 female patients with a mean age of 84 ± 4 years.
There were no significant differences in terms of age, sex, body surface area,
body mass index, past medical history, serum creatinine, medications, and
transthoracic echocardiographic data between patients with PPM and those
without PPM before TAVR. As for 123I-MIBG parameters before TAVR,
patients without PPM had higher early H/M ratio and WR than those with
PPM.

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Patient Characteristics Before and After Transcatheter Aortic Valve
Replacement in Relation to Patient-Prosthesis Mismatch
The rate of overall and severe PPM among the study population was 39% (n
= 17) and 11% (n = 5), respectively. Significant improvements in AVA, peak
pressure gradient, and mean pressure gradient after TAVR were observed in
patients with and without PPM. Those without PPM exhibited significant
regression in LVMI after TAVR, whereas those with PPM did not. Patients
without PPM exhibited significant improvements in delayed H/M ratio and
WR after TAVR, while those with PPM did not.

Factors Associated with Improvements in 123I-Metaiodobenzylguanidine
Parameters
Multivariable linear regression analysis revealed PPM was a negative
predictor of improvement in delayed H/M ratio. Furthermore, PPM and
baseline WR were independent predictors of improvement in WR.

Discussion

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This investigation of the impact of PPM after TAVR on changes in CSN
function using 123I-MIBG scintigraphy demonstrates the following: (1)
delayed H/M ratio and WR improve significantly after TAVR for patients
without PPM, whereas patients with PPM do not experience these
improvements, and (2) PPM is a negative predictor of improvements in
delayed H/M ratio and WR in patients undergoing TAVR.
Although the use of TAVR is expanding rapidly, the risk of PPM remains a
potential limitation of the procedure.
Although previous studies have reported the early effects of TAVR on CSN
function using 123I-MIBG scintigraphy, the impact of PPM after TAVR on
changes in CSN function is not well established.
Our findings of the impact of PPM after TAVR on changes in CSN function
may be explained by the association between PPM and reduced hemodynamic
improvement after TAVR. We found that patients with PPM experienced less
favorable changes after TAVR compared to those without PPM including
lower AVA, higher peak and mean pressure gradients, and limited LVMI
regression. Similar findings have been reported in previous studies. The small
indexed effective orifice area and its residual high pressure gradient may

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suppress improvements in 123I-MIBG parameters.
In conclusion, our findings suggest that delayed H/M ratio and WR improve
significantly after TAVR for patients who do not experience PPM. Because of
the negative effects in terms of improvement in 123I-MIBG parameters,
strategies to prevent or minimize PPM are important, especially for patients
with CSN overactivation.

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