J Artif Organs DOI 10.1007/s10047-014-0769-x
ORIGINAL ARTICLE
Artificial Valve
Cardiac energetics analysis after aortic valve replacement with 16-mm ATS mechanical valve Tomoki Ushijima • Yoshihisa Tanoue • Takayuki Uchida • Sho Matsuyama • Takashi Matsumoto • Ryuji Tominaga
Received: 16 October 2013 / Accepted: 30 April 2014 Ó The Japanese Society for Artificial Organs 2014
Abstract The 16-mm ATS mechanical valve is one of the smallest prosthetic valves used for aortic valve replacement (AVR) in patients with a very small aortic annulus, and its clinical outcomes are reportedly satisfactory. Here, we analyzed the left ventricular (LV) performance after AVR with the 16-mm ATS mechanical valve, based on the concept of cardiac energetics analysis. Eleven patients who underwent AVR with the 16-mm ATS mechanical valve were enrolled in this study. All underwent echocardiographic examination at three time points: before AVR, approximately 1 month after AVR, and approximately 1 year after AVR. LV contractility (end-systolic elastance [Ees]), afterload (effective arterial elastance [Ea]), and efficiency (ventriculoarterial coupling [Ea/Ees] and the stroke work to pressure–volume area ratio [SW/PVA]) were noninvasively measured by echocardiographic data and blood pressure measurement. Ees transiently decreased after AVR and then recovered to the pre-AVR level at the one-year follow-up. Ea significantly decreased in a stepwise manner. Consequently, Ea/Ees and SW/PVA were also significantly improved at the one-year follow-up compared with those before AVR. The midterm LV performance after AVR with the 16-mm ATS mechanical valve was satisfactory. AVR with the 16-mm ATS mechanical valve is validated as an effective treatment T. Ushijima T. Uchida S. Matsuyama T. Matsumoto Department of Cardiovascular Surgery, Aso Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka 820-8505, Japan T. Ushijima Y. Tanoue (&) R. Tominaga (&) Department of Cardiovascular Surgery, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan e-mail: [email protected] R. Tominaga e-mail: [email protected]
for patients with a very small aortic annulus. The cardiac energetics variables, coupling with the conventional hemodynamic variables, can contribute to a better understanding of the patients’ clinical conditions, and those may serve as promising indices of the cardiac function. Keywords Aortic valve replacement Small aortic annulus Cardiac function
Introduction Several surgical techniques of aortic valve replacement (AVR) in patients with a small aortic annulus have been developed, such as aortic annular enlargement [1–3] and stentless valve implantation by the full-root method [4]. High-performance prosthetic valves that obtain an adequate effective orifice area have also been developed and clinically introduced. The 16-mm ATS mechanical valve (ATS Medical Inc., Minneapolis, MN) is one of the smallest prosthetic valves used for AVR in patients with a very small aortic annulus, and its clinical outcomes are reportedly satisfactory [5, 6]. The cardiac energetics analysis, including end-systolic elastance (Ees), effective arterial elastance (Ea), and ventriculoarterial coupling (Ea/Ees) and the stroke work to pressure–volume area ratio (SW/PVA), enables analysis of left ventricular (LV) contractility, afterload, and ventricular efficiency, respectively [7–9]. We reported that Ees and Ea could be approximated by LV volume and arterial blood pressure (BP) obtained from the cardiac catheterization in previous basic and clinical studies [10–15]. We subsequently calculated these variables with an echocardiographic volume calculation and BP measurement by the Korotkoff technique using the manchette method, and this
123
J Artif Organs
modification was clinically applied to various acquired and congenital heart diseases [16–20]. Here, we focus on AVR with the 16-mm ATS mechanical valve, one of the smallest mechanical valves, and apply this modification to analysis of the postoperative LV performance. The purpose of this study was to demonstrate the validity of this valve implantation in patients with a very small aortic annulus, based on the concept of cardiac energetics analysis.
Table 1 Baseline characteristics of all patients Characteristics
n = 11
Sex (male, female)
0, 11
Age (median, years)
81.6 (58.3–89.1)
Body surface area (mean, m2)
1.33 ± 0.15
Etiology of aortic valve disease Aortic stenosis
7
Aortic stenosis with regurgitation
4
Bicuspid aortic valve
2
Comorbidities
Materials and methods
Ischemic heart disease, Previous PCI
3, 1
Other valvular lesion (mitral and/or tricuspid valve)
3
Patient population
Peripheral artery disease
2
From January 2005 to December 2010, a total of 146 consecutive patients (91 mechanical valves, 55 bioprosthetic valves) underwent AVR at Aso Iizuka Hospital. Of 91 patients who underwent AVR with a mechanical valve, 16 (all female) underwent implantation with the 16-mm ATS mechanical valve. Five patients were excluded from this study; two patients died within one year after AVR due to noncardiac cause, and all the other three patients were alive at the time of writing this report, who could not be analyzed the cardiac energetics due to their data deficits. Eleven patients were enrolled in this study. The patients’ baseline characteristics are summarized in Table 1. All patients’ preoperative condition was determined to be sufficient, and all underwent the elective operation. The clinical and operative records of enrolled patients were retrospectively reviewed, and the individual patients were not identified. This study was approved by our institutional committee on human research. Operative techniques and postoperative anticoagulant therapy A median sternotomy was performed in all patients, and standard cardiopulmonary bypass was established. The valve size was determined based on the aortic annulus diameter as measured with a sizer. A 16-mm ATS-Advanced Performance (AP) valve was used in seven patients, and a 16-mm ATS-AP360 valve was used in four patients. The mechanical valve was implanted at an intra-annular position (10 patients) or supra-annular position (1 patient). Valve implantation at the intra-annular position was the first-choice standard technique in our institution; only when aortic annulus is too small to allow for implantation at the intra-annular position, the prosthetic valve was implanted at the supra-annular position. All operations were conducted without aortic annular enlargement. Isolated AVR was performed in eight patients. Concomitant procedures were required in three patients; coronary artery bypass grafting in two patients, mitral
123
Chronic obstructive pulmonary disease
2
On-hemodialysis
1
NYHA functional class (mean) I, II, III, IV
2.3 ± 0.7 1, 6, 4, 0
Preoperative echocardiographic data Aortic valve area (cm2)
0.57 ± 0.21
Peak pressure gradient across the aortic valve (mmHg) LV ejection fraction (%)
98.9 ± 40.5
2
LV mass index (g/m )
64.7 ± 7.5 167.9 ± 36.7
Data are presented as the number of patients or as the mean ± SD or the median value (range) LV left ventricular, NYHA New York Heart Association, PCI percutaneous coronary intervention
annuloplasty for severe mitral regurgitation in one patient, tricuspid annuloplasty for severe tricuspid regurgitation in one patients, and pulmonary vein isolation for paroxysmal atrial fibrillation in one patient. Anticoagulant therapy was administered to all patients, and prothrombin time was targeted at an international normalized ratio of 2.0–3.0. Antiplatelet therapy was simultaneously administered in all patients. Definition of prosthesis-patient mismatch A reference effective orifice area (EOA) index was defined as a commercially available EOA normalized the body surface area (BSA), and a prosthesis-patient mismatch (PPM) was defined as the reference EOA index of 0.85 cm2/ m2 or less as described in previous papers [21, 22]. Hemodynamic evaluation by pressure gradient, ejection fraction, and LV mass All echocardiographic examinations were performed by skilled examiners with either Sonos 5500 (Philips
J Artif Organs
Electoronics, Andover, MA) or Vivid 7 (GE Medical System, Milwaukee, WI). All patients underwent transthoracic echocardiographic examinations before AVR, after AVR (approximately 1 month after surgery), and at a one-year follow-up (approximately one year after surgery). The data were obtained from two-dimensional M-mode measurement and Doppler echocardiographic measurement, and the peak pressure gradient across the aortic valve (peak PG), the LV ejection fraction (LVEF), and the LV mass were calculated. The peak PG was calculated by the Bernoulli formula from maximum velocity across the aortic valve in systole [23]. The LV end-systolic volume (LVESV) and LV end-diastolic volume (LVEDV) were calculated by the Teichholz method [24]. The LVEF was calculated as follows: LVEF = (1 – LVESV/ LVEDV) 9 100 (%) [25]. The LV mass was calculated by the Devereux formula [25], and the obtained value was normalized by the BSA to define the LV mass index (LVMI). Changes in these conventional hemodynamic variables were investigated at the three above-described time points.
cardiac function by this approximation method is 5.07 ± 2.03 mmHg/ml/m2, Ea is 3.01 ± 0.76 mmHg/ml/ m2, Ea/Ees is 0.66 ± 0.26, and SW/PVA is 75.8 ± 6.7 %, respectively [16]. Statistical analysis Continuous variables were expressed as the mean ± SD or median value and were compared by unpaired t tests. Repeated measures one-way analysis of variance (RMANOVA) was used for the variables at the three measured time points (before AVR, after AVR, and at a one-year follow-up) in all patients, and the Student–Newman–Keuls test was used as a post hoc test. A p value of \0.05 was considered to be statistically significant. GraphPad Prism 5.0 (GraphPad Software Inc., San Diego, CA) was used for all statistical analysis.
Results Follow-up after AVR
Cardiac energetics analysis with approximation method The cardiac energetics variables include Ees, Ea, Ea/Ees, and SW/PVA. Ees represents the load-independent index of contractility, and Ea represents the index of afterload. Ea/Ees represents ventriculoarterial coupling between the LV and the arterial system [7]. Ea/Ees and SW/PVA are the indices of ventricular efficiency [26]. The theoretical background and the validity of approximation method were particularly described in ‘‘Appendix’’. End-systolic elastance and Ea were calculated with the same approximation formula as previously reported [16– 20]: Ees = corrected mean BP/minimal LV volume and Ea = maximal LV pressure/(maximal LV volume – minimal LV volume). In this study, the LV volume was obtained from the echocardiographic data, and the arterial BP was measured by the Korotkoff technique using the manchette method. The maximal LV volume was defined as identical with the LVEDV, and the minimal LV volume was defined as identical with the LVESV. Each LV volume was normalized by the BSA. The maximal LV pressure was corrected by the peak PG; maximal LV pressure = arterial systolic BP ? peak PG. The corrected mean BP was calculated from the maximal LV pressure and the arterial diastolic BP; corrected mean BP = (maximal LV pressure ? 2 9 arterial diastolic BP)/3. Ea/Ees was the ratio of Ea to Ees. SW/PVA was calculated with the following theoretical formula: SW/PVA = 1/(1 ? 0.5 Ea/Ees) [26]. Changes in these cardiac energetic variables were investigated at the three above-described time points. As previously described, Ees of patients with normal
The mean follow-up period was 35.9 ± 17.5 months, and the longest follow-up period was 73.3 months. There were two late mortalities during the follow-up period. One patient died of progressive heart failure due to mitral regurgitation 12.2 months after AVR, and another patient died of a noncardiac cause 28.2 months after AVR. No aortic valve-related adverse events occurred during all enrolled patients’ follow-up period. Changes in conventional hemodynamic variables after AVR Conventional hemodynamic variables include peak PG, LVEF, and LVMI. Comparisons of these variables obtained from the echocardiographic data among the three time points are shown in Fig. 1a–c. The peak PG significantly decreased after AVR and at the one-year follow-up (from 98.9 ± 40.5 to 43.6 ± 15.6 and 38.9 ± 9.4 mmHg, p \ 0.0001, by RM-ANOVA). The LVEF hardly changed after AVR, but was significantly improved at the one-year follow-up (from 64.7 ± 7.5 to 64.0 ± 9.4 and 72.9 ± 7.6 %, p = 0.011, by RMANOVA). The LVMI also hardly changed after AVR, but significantly decreased at the one-year follow-up (from 167.9 ± 36.7 to 152.8 ± 44.3 and 126.2 ± 35.3 g/ m2, p = 0.004, by RM-ANOVA). The peak PG, LVEF, and LVMI were significantly improved at the one-year follow-up compared with those before AVR (p \ 0.001, p \ 0.05, and p \ 0.01, respectively, by the post hoc test).
123
J Artif Organs
B LVEF [%]
A Peak PG [mmHg]
C LVMI [g/m2] 300
90 150
250
80 ‡,
100
200
70
150
60 50
*
†,
100
*
50 50 0 Before AVR
After AVR
At 1-year follow-up
Before AVR
D Ees [mmHg/ml/m2] 10
After AVR
At 1-year follow-up
Before AVR
E Ea [mmHg/ml/m2]
After AVR
At 1-year follow-up
F Ea/Ees
G SW/PVA [%]
2.0
90
1.5
80
10 ‡,
70 5
1.0
‡
5
†
‡,
60
0.5 50 0
0
0 Before AVR
After AVR
At 1-year follow-up
Before AVR
After AVR
At 1-year follow-up
* p < 0.001, † p < 0.01, ‡ p < 0.05 vs. before AVR;
Before AVR
After AVR
At 1-year follow-up
Before AVR
After AVR
At 1-year follow-up
p < 0.05 vs. after AVR.
Fig. 1 Changes in conventional hemodynamic variables (a–c) and cardiac energetics variables (d–g) at the three time points (Before AVR, approximately one month after AVR [After AVR], and approximately one year after AVR [At one-year follow-up]). a The peak PG significantly decreased after AVR and at the one-year follow-up. b, c The LVEF (b) and the LVMI (c) hardly changed after AVR, but both were significantly improved at the one-year follow-up. d Ees transiently decreased after AVR and then recovered to the preAVR value at the one-year follow-up. e Ea significantly decreased in a stepwise manner. f, g Ea/Ees (f) and SW/PVA (g) were significantly
improved at the one-year follow-up compared with those before AVR. Closed circles and solid lines indicate the mean of all patients; bars indicate the standard deviation. The Student–Newman–Keuls test was used as a post hoc test. AVR aortic valve replacement, peak PG peak pressure gradient across the aortic valve, LVEF left ventricular ejection fraction, LVMI left ventricular mass index, Ees end-systolic elastance, Ea effective arterial elastance, Ea/Ees ventriculoarterial coupling, SW/PVA stroke work to pressure–volume area ratio
Cardiac energetics analysis after AVR
between Ea before AVR and that at the one-year follow-up (p \ 0.01, by the post hoc test). Ea/Ees and SW/PVA were significantly improved (Ea/Ees, from 1.1 ± 0.4 to 1.0 ± 0.4 and 0.7 ± 0.3, p = 0.020, by RM-ANOVA; SW/ PVA, from 66.3 ± 8.5 to 67.9 ± 8.3 and 75.6 ± 7.6 %, p = 0.011, by RM-ANOVA). These values were recovered to the normal level at the one-year follow-up. There was also a statistically significant difference between these values before AVR and at the one-year follow-up (p \ 0.05 for both, by the post hoc test). Further, comparison of these variables between the patients group with or without PPM at the one-year follow-up was shown in Table 3. There was no significant difference between the two groups.
Comparisons of the cardiac energetics variables among the three time points are shown in Fig. 1d–g. The measured parameters for calculation of Ees and Ea are presented in Table 2. Ees did not significantly change among the three time points (from 6.3 ± 3.0 to 5.2 ± 2.1 and 6.9 ± 2.3 mmHg/ml/m2, p = 0.15, by RM-ANOVA). Ees transiently decreased after AVR and then recovered to the pre-AVR value at the one-year follow-up. Ea significantly decreased in a stepwise manner (from 5.8 ± 1.1 to 4.6 ± 1.3 and 4.2 ± 1.2 mmHg/ml/m2, p = 0.005, by RMANOVA). There was a statistically significant difference
123
J Artif Organs Table 2 Measured parameters for calculation of cardiac energetics variables Parameters Heart rate (bpm)
Before AVR
After AVR
At one-year follow-up
68.8 ± 12.6
75.7 ± 13.4
63.6 ± 14.6
128.4 ± 26.1
121.4 ± 11.4
134.5 ± 34.8
Arterial diastolic BP (mmHg)
68.9 ± 9.1
64.5 ± 6.9
64.2 ± 16.4
Peak PG across the aortic valve (mmHg)
98.9 ± 40.5
Maximal LV pressure (mmHg)
227.3 ± 40.3
165.0 ± 15.7
173.5 ± 40.7
Corrected mean BP (mmHg)
121.7 ± 15.4
98.0 ± 6.3
100.6 ± 23.8
Maximal LV volume (ml/m2)
63.5 ± 16.9
61.4 ± 20.5
59.5 ± 14.8
Minimal LV volume (ml/m2)
23.3 ± 10.3
22.9 ± 12.8
16.7 ± 8.2
Arterial systolic BP (mmHg)
Table 3 Comparison of cardiac energetics variables and associated parameters between the patients group with or without PPM at the midterm follow-up Cardiac energetics variables and associated parameters Reference EOA index (cm2/m2)
With PPM (n = 3) 0.80 ± 0.06
Without PPM (n = 8) 0.95 ± 0.08*
Cardiac energetics variables
43.6 ± 15.6*
38.9 ± 9.4*
Ees (mmHg/ml/m2)
7.5 ± 2.2
6.7 ± 2.5
Ea (mmHg/ml/m2)
4.5 ± 0.2
4.1 ± 1.4
Ea/Ees SW/PVA (%)
The maximal LV pressure was corrected by the peak PG across the aortic valve; maximal LV pressure = peak PG ? arterial systolic BP. The corrected mean BP was calculated from the maximal LV pressure and the arterial diastolic BP; corrected mean BP = (maximal LV pressure ? 2 9 arterial diastolic BP)/3. The maximal LV volume and the minimal LV volume were defined as identical with the LV enddiastolic volume and the LV end-systolic volume calculated by echocardiography, respectively, and each LV volume was normalized by the body surface area AVR aortic valve replacement, BP blood pressure, PG pressure gradient, LV left ventricular * p \ 0.001 versus before AVR;
p \ 0.01 versus before AVR
0.7 ± 0.4 75.4 ± 8.8
Associated parameters Heart rate (bpm)
Data are presented as the mean ± SD
0.6 ± 0.1 76.0 ± 4.4
Arterial systolic BP (mmHg)
55.3 ± 7.1
66.8 ± 15.7
141.0 ± 24.9
132.1 ± 39.1
Arterial diastolic BP (mmHg)
66.3 ± 8.5
63.4 ± 19.0
Peak PG across the aortic valve (mmHg)
40.4 ± 9.2
38.4 ± 10.0
Maximal LV pressure (mmHg)
181.4 ± 27.2
170.5 ± 46.0
Corrected mean BP (mmHg)
104.7 ± 14.2
99.1 ± 27.2
Maximal LV volume (ml/m2)
55.4 ± 12.9
61.0 ± 16.0
2
Minimal LV volume (ml/m ) LV ejection fraction (%) LV mass index (g/m2)
15.1 ± 5.5
17.3 ± 9.3
73.4 ± 4.2
72.7 ± 8.7
113.4 ± 18.5
131.0 ± 39.9
Data are presented as the mean ± SD The reference EOA index was defined as a commercially available EOA normalized the body surface area, and a PPM was defined as a reference EOA index of 0.85 cm2/m2 or less BP blood pressure, Ees end-systolic elastance, Ea effective arterial elastance, Ea/Ees the ratio of Ea to Ees, SW/PVA the stroke work to pressure–volume area ratio, EOA effective orifice area, PPM prosthesis-patient mismatch, LV left ventricular * p \ 0.05 versus with PPM group
Discussion After AVR with the 16-mm ATS mechanical valve, the LV contractility (Ees) did not significantly change, and the afterload (Ea) was significantly reduced in a stepwise manner. The ventricular efficiency (Ea/Ees and SW/PVA) was also significantly improved. This tendency was verified approximately one year after AVR. AVR with the 16-mm ATS mechanical valve in patients with a very small aortic annulus was validated with respect to the significant improvement of LV performance at the postoperative midterm. Improvement in ventricular efficiency at midterm after AVR with 16-mm ATS mechanical valve In this study, the LV contractility transiently decreased after AVR compared with that before AVR and then recovered to the pre-AVR value at the one-year follow-up. As shown in Table 2, approximately one month after AVR, an abrupt decrease in LV pressure, which resulted from the
release of the aortic valve stenotic lesion, would bring about a simultaneous decrease in contractility. Subsequently, approximately one year after AVR, the LV contractility recovery was achieved due to reduction of minimal LV volume. The afterload reduction in a stepwise manner resulted from an initial decrease in LV pressure due to the release of the aortic valve stenotic lesion and the following reduction of minimal volume. Consequently, cooperation between contractility recovery and afterload reduction can contribute to the improvement in ventricular efficiency at the midterm follow-up, whereas this cooperation cannot be obtained in the short-term postoperative period. These results are similar to our previous paper which has described the LV performance in isolated AVR for aortic stenosis [16, 20]. A persistent and proper postoperative afterload reduction treatment is important until LV adaptation due to reverse remodeling is achieved. Thereafter, the improvement in ventricular efficiency could be verified at the postoperative midterm, as shown in Fig. 1f, g.
123
J Artif Organs
Significance of cardiac energetics analysis after AVR with 16-mm ATS mechanical valve So far, the absence of PPM, the cardiac function improvement, and the LV mass regression have been widely used to evaluate the effectiveness of AVR. The impact of PPM on a prognosis of patients who underwent AVR is still controversial [21, 22], but its effectiveness is always associated with its potential of PPM, especially when discussing AVR in patients with a very small aortic annulus. In this study, the peak PG at one year after AVR was 38.9 ± 9.4 mmHg, which was maintained until the most recent follow-up. This value was almost equivalent to that in previous reports [5, 6]. Of this study patients, three patients had the reference EOA index of less than 0.85 cm2/m2, in whom neither cardiac events nor LV functional impairment was found during the follow-up period. The LVEF and the LV mass can conveniently provide good practical informations. However, the LVEF, which represents the load-dependent index of contractility, does not explain the LV contractility and the afterload separately; the LV mass, which represents the index of LV hypertrophy, does not also associated with the concept of ventricular efficiency. On the other hand, the cardiac energetics analysis can provide additional practical informations over conventional hemodynamic variables; it can simultaneously explain the load-independent LV contractility and the afterload separately. The LVMI is available as a static hemodynamic index, whereas the ventricular efficiency (Ea/Ees and SW/PVA) can play a role as a dynamic hemodynamic index. Additionally, the cardiac energetics analysis can make it easy to understand the above-described process of contractility recovery and afterload reduction. These understandings are beneficial for postoperative optimal medical treatment (e.g., diagnosis of whether the cardiac functional impairment resulted from systolic dysfunction or afterload mismatch). The cardiac energetics analysis does not contradict the conventional understandings and has an additional role for a better understanding of the patients’ clinical conditions, coupling with conventional hemodynamic variables. In terms of this point, the cardiac energetics variables may serve as promising indices of the cardiac function. Contribution of the 16-mm ATS mechanical valve to simplification of operative procedures Aortic valve replacement with additional aortic annular enlargement and stentless valve implantation by the fullroot method to avoid PPM is associated with major invasiveness due to its complex manipulations, which can cause certain complications. The median age of enrolled patients was 81.6 years, and six patients were octogenarians.
123
Almost all of these patients had some associated comorbidities, as well as aortic valve disease, as shown in Table 1. In addition, almost all patients had not only aortic valve lesions, but also a severely calcified sinus of Valsalva and ascending aorta, which often made it difficult to conduct the annular enlargement. The 16-mm ATS mechanical valve implantation can simplify the operative procedure and minimize the operative invasiveness, which can lead to a decrease in the incidence of operative complications. Operative strategy for aortic valve lesions in our institution In our institution, AVR with a bioprosthetic valve has been performed as the first-choice standard technique for aged patients to avoid the major complications associated with anticoagulant therapy. No bleeding events were found in this enrolled patients, but aged patients have potential bleeding risks associated with anticoagulant therapy. Only when aortic annulus is too small to allow for implantation of the smallest bioprosthetic valve, we will choose the smallest mechanical valve. This study verified the satisfactory midterm LV performance after AVR with the 16-mm ATS mechanical valve. A 16-mm ATS mechanical valve is an effective prosthetic valve in patients with a very small aortic annulus, and the use of this valve should be considered in patients whose small aortic annulus cannot allow for the smallest bioprosthetic valve implantation. Study limitations This retrospective study has some inherent limitations. First, this study included a small group and heterogenous population. Patients who undergo AVR with a 16-mm mechanical valve constitute a rare and limited population, and some patients were required concomitant procedure. Second, the two types of 16-mm mechanical valve, ATSAP valve and ATS-AP360 valve, were used for AVR. ATS-AP360 valve is the next generation prosthesis to ATS-AP valve, whose shape of sewing cuff is modified and allows for valve implantation in patients with a smaller aortic annulus. Third, the LV volume was calculated by the Teichholz method. Simpson’s method is more suitable than the Teichholz method for LV volume calculation. Also, the LV pressure was not precisely corrected because the PG value was possibly overestimated. Fourth, the approximation of Ees and Ea was not as accurate as measurements obtained from a conductance catheter system. This approximation method has so far only been validated in the animal model where cardiac function is normal [10] and has several modifications as described in ‘‘Appendix’’. Last, the correlation between ventricular efficiency improvement and reverse remodeling achievement was not
J Artif Organs
elucidated due to a small group. However, we believe that these limitations are acceptable for cardiac energetics analysis and that these limitations do not detract from the validity of our conclusions. The future study subjected the larger group can elucidate the more remarkable significance of cardiac energetics analysis.
Conclusion The midterm LV performance after AVR with the 16-mm ATS mechanical valve was satisfactory. The validity of this valve implantation was elucidated based on the concept of cardiac energetics analysis. The cardiac energetics variables, coupling with the conventional hemodynamic variables, can contribute to a better understanding of the patients’ clinical conditions, and those may serve as promising indices of the cardiac function. Conflict of interest There is no conflict of interest or disclosure for any of the authors with any companies/organizations whose product/ services discussed in this manuscript.
Appendix Theoretical background The cardiac energetics variables include Ees, Ea, and Ea/ Ees and SW/PVA. Ees represents the load-independent index of contractility; Ea represents the index of afterload; and Ea/Ees and SW/PVA are the indices of ventricular efficiency. As particularly described in previous investigations, Ees is the slope of the end-systolic pressure–volume relation [8], and Ea is the ratio of end-systolic pressure to stroke volume [9]. Ea/Ees represents ventriculoarterial coupling between the LV and the arterial system [7]. SW represents the external mechanical work, and PVA represents the total mechanical energy generated by ventricular contraction. The ratio of SW to PVA can be understood as the energy efficiency. These variables are actually determined from the multiple LV pressure–volume loops with a conductance catheter system. Furthermore, SW/PVA can be theoretically predicted by Ees and Ea as follows: SW/ PVA = 1/(1 ? 0.5 Ea/Ees) [26]. Validity of approximated Ees and Ea We previously described the approximation methods of Ees and Ea as follows: approximated Ees = mean arterial pressure/minimal ventricular volume; approximated Ea = maximal ventricular pressure/(maximal ventricular volume – minimal ventricular volume) [10]. With this modification, the cardiac energetics variables can be easily
calculated.The important point is that end-systolic ventricular volume and end-diastolic ventricular volume according to the pressure–volume loop are not same as minimal ventricular volume and maximal ventricular volume, respectively. Normally, end-systolic ventricular volume is larger than minimal ventricular volume and end-diastolic ventricular volume is lower than maximal ventricular volume. Another important point is that endsystolic ventricular pressure is smaller than maximal ventricular pressure. In these points, the present approximated Ees and Ea are not precisely identical with Ees and Ea measured with a conductance catheter system. In particular, the approximated Ees is calculated not as the ratio of end-systolic pressure to end-systolic ventricular volume, but as the ratio of mean arterial blood pressure to minimal ventricular volume, and therefore, the volume intercept is not defined as zero [15]. The high correlations between Ees and the approximated Ees and between Ea and the approximated Ea were experimentally validated in the basic study using a canine right heart bypass preparation with a conductance catheter system [10]. This modification has the advantages that ventricular volume and blood pressure are measured with the cardiac catheterization, which enables the cardiac energetics analysis in various clinical situations [10–15]. Further modifying this modification in the recent study, the LV performance has been analyzed with the echocardiographic ventricular volume calculation and noninvasively measured blood pressure [16–20]. This modification can be the promising analysis method of ventricular efficiency.
References 1. Nicks R, Cartmill T, Bernstein L. Hypoplasia of the aortic root. The problem of aortic valve replacement. Thorax. 1970; 25:339–46. 2. S, Imai Y, Iida Y, Nakajima M, Tatsuno K. A new method for prosthetic valve replacement in congenital aortic stenosis associated with hypoplasia of the aortic valve ring. J Thorac Cardiovasc Surg. 1975;70:909–17. 3. Manouguian S, Seybold-Epting W. Patch enlargement of the aortic valve ring by extending the aortic incision into the anterior mitral leaflet. New operative technique. J Thorac Cardiovasc Surg. 1979;78:402–12. 4. Ennker IC, Albert A, Dalladaku F, Rosendahl U, Ennker J, Florath I. Midterm outcome after aortic root replacement with stentless porcine bioprostheses. Eur J Cardiothorac Surg. 2011;40:429–34. 5. Nakamura Y, Nakano K, Tagusari O, Kataoka G, Seike Y, Domoto S, Ito Y. An alternative option for elderly patients with a small aortic annulus: the 16 mm ATS valve. J Heart Valve Dis. 2009;18:691–7. 6. Kobayashi Y, Fukushima Y, Hayase T, Kojima K, Endo G. Clinical outcome of aortic valve replacement with 16-mm ATSadvanced performance valve for small aortic annulus. Ann Thorac Surg. 2010;89:1195–9.
123
J Artif Organs 7. Burkhoff D, Sagawa K. Ventricular efficiency predicted by an analytical model. Am J Physiol. 1986;250:R1021–7. 8. Suga H. Ventricular energetics. Physiol Rev. 1990;70:247–77. 9. Sunagawa K, Maughan WL, Burkhoff D, Sagawa K. Left ventricular interaction with arterial load studied in isolated canine ventricle. Am J Physiol. 1983;245:H773–80. 10. Tanoue Y, Sese A, Ueno Y, Joh K, Hijii T. Bidirectional Glenn procedure improves the mechanical efficiency of a total cavopulmonary connection in high-risk fontan candidates. Circulation. 2001;103:2176–80. 11. Tanoue Y, Ando H, Fukumura F, Umesue M, Uchida T, Taniguchi K, Tanaka J. Ventricular energetics in endoventricular circular patch plasty for dyskinetic anterior left ventricular aneurysm. Ann Thorac Surg. 2003;75:1205–9. 12. Tanoue Y, Sese A, Imoto Y, Joh K. Ventricular mechanics in the bidirectional glenn procedure and total cavopulmonary connection. Ann Thorac Surg. 2003;76:562–6. 13. Tanoue Y, Kado H, Maeda T, Shiokawa Y, Fusazaki N, Ishikawa S. Left ventricular performance of pulmonary atresia with intact ventricular septum after right heart bypass surgery. J Thorac Cardiovasc Surg. 2004;128:710–7. 14. Tanoue Y, Kado H, Shiokawa Y, Fusazaki N, Ishikawa S. Midterm ventricular performance after Norwood procedure with right ventricular-pulmonary artery conduit. Ann Thorac Surg. 2004;78:1965–71. 15. Tanoue Y, Kado H, Ushijima T, Tominaga R. Consequences of a hypertensive right ventricle on left ventricular performance of patients with pulmonary atresia and intact ventricular septum after right heart bypass surgery. Prog Pediatr Cardiol. 2010;29:43–8. 16. Tanoue Y, Maeda T, Oda S, Baba H, Oishi Y, Tokunaga S, Nakashima A, Tominaga R. Left ventricular performance in aortic valve replacement. Interact CardioVasc Thorac Surg. 2009;9:255–9. 17. Tanoue Y, Tomita Y, Morita S, Tominaga R. Ventricular energetics in aortic root replacement for annuloaortic ectasia with aortic regurgitation. Heart Vessels. 2009;24:41–5. 18. Imasaka KI, Tomita Y, Tanoue Y, Tominaga R, Tayama E, Onitsuka H, Ueda T. Early mitral valve surgery for chronic severe mitral regurgitation optimizes left ventricular performance and left ventricular mass regression. J Thorac Cardiovasc Surg. 2012;146:61–6.
123
19. Nagata H, Ihara K, Yamamura K, Tanoue Y, Shiokawa Y, Tominaga R, Hara T. Left ventricular efficiency after ligation of patent ductus arteriosus for premature infants. J Thorac Cardiovasc Surg. 2013;146:1353–8. 20. Tanoue Y, Oishi Y, Sonoda H, Nishida T, Nakashima A, Tominaga R. Left ventricular performance after aortic valve replacement in patients with low ejection fraction. J Artif Organs. 2013;15:444–50. 21. Jamieson WR, Ye J, Higgins J, Cheung A, Fradet GJ, Skarsgard P, Germann E, Chan F, Lichtenstein SV. Effect of prosthesispatient mismatch on long-term survival with aortic valve replacement: assessment to 15 years. Ann Thorac Surg. 2010;89:51–9. 22. Head SJ, Mokhles MM, Osnabrugge RL, Pibarot P, Mack MJ, Takkenberg JJ, Bogers AJ, Kappetein AP. The impact of prosthesis-patient mismatch on long-term survival after aortic valve replacement: a systematic review and meta-analysis of 34 observational studies comprising 27186 patients with 133141 patient-years. Eur Heart J. 2012;33:1518–29. 23. Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, Griffin BP, Iung B, Otto CM, Pellikka PA, Quin˜ones M. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. J Am Soc Echocardiogr. 2009;22:1–23. 24. Teichholz LE, Kreulen T, Herman MV, Gorlin R. Problems in echocardiographic volume determinations: echocardiographicangiographic correlations in the presence of absence of asynergy. Am J Cardiol. 1976;37:7–11. 25. Lang RM, Bierig M, Devereux RB, Flachskampf M, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18:1440–63. 26. Nozawa T, Yasumura Y, Futaki S, Tanaka N, Uenishi M, Suga H. Efficiency of energy transfer from pressure-volume area to external mechanical work increases with contractile state and decreases with afterload in the left ventricle of the anesthetized closed-chest dog. Circulation. 1988;77:1116–24.
ORIGINAL ARTICLE
Artificial Valve
Cardiac energetics analysis after aortic valve replacement with 16-mm ATS mechanical valve Tomoki Ushijima • Yoshihisa Tanoue • Takayuki Uchida • Sho Matsuyama • Takashi Matsumoto • Ryuji Tominaga
Received: 16 October 2013 / Accepted: 30 April 2014 Ó The Japanese Society for Artificial Organs 2014
Abstract The 16-mm ATS mechanical valve is one of the smallest prosthetic valves used for aortic valve replacement (AVR) in patients with a very small aortic annulus, and its clinical outcomes are reportedly satisfactory. Here, we analyzed the left ventricular (LV) performance after AVR with the 16-mm ATS mechanical valve, based on the concept of cardiac energetics analysis. Eleven patients who underwent AVR with the 16-mm ATS mechanical valve were enrolled in this study. All underwent echocardiographic examination at three time points: before AVR, approximately 1 month after AVR, and approximately 1 year after AVR. LV contractility (end-systolic elastance [Ees]), afterload (effective arterial elastance [Ea]), and efficiency (ventriculoarterial coupling [Ea/Ees] and the stroke work to pressure–volume area ratio [SW/PVA]) were noninvasively measured by echocardiographic data and blood pressure measurement. Ees transiently decreased after AVR and then recovered to the pre-AVR level at the one-year follow-up. Ea significantly decreased in a stepwise manner. Consequently, Ea/Ees and SW/PVA were also significantly improved at the one-year follow-up compared with those before AVR. The midterm LV performance after AVR with the 16-mm ATS mechanical valve was satisfactory. AVR with the 16-mm ATS mechanical valve is validated as an effective treatment T. Ushijima T. Uchida S. Matsuyama T. Matsumoto Department of Cardiovascular Surgery, Aso Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka 820-8505, Japan T. Ushijima Y. Tanoue (&) R. Tominaga (&) Department of Cardiovascular Surgery, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan e-mail: [email protected] R. Tominaga e-mail: [email protected]
for patients with a very small aortic annulus. The cardiac energetics variables, coupling with the conventional hemodynamic variables, can contribute to a better understanding of the patients’ clinical conditions, and those may serve as promising indices of the cardiac function. Keywords Aortic valve replacement Small aortic annulus Cardiac function
Introduction Several surgical techniques of aortic valve replacement (AVR) in patients with a small aortic annulus have been developed, such as aortic annular enlargement [1–3] and stentless valve implantation by the full-root method [4]. High-performance prosthetic valves that obtain an adequate effective orifice area have also been developed and clinically introduced. The 16-mm ATS mechanical valve (ATS Medical Inc., Minneapolis, MN) is one of the smallest prosthetic valves used for AVR in patients with a very small aortic annulus, and its clinical outcomes are reportedly satisfactory [5, 6]. The cardiac energetics analysis, including end-systolic elastance (Ees), effective arterial elastance (Ea), and ventriculoarterial coupling (Ea/Ees) and the stroke work to pressure–volume area ratio (SW/PVA), enables analysis of left ventricular (LV) contractility, afterload, and ventricular efficiency, respectively [7–9]. We reported that Ees and Ea could be approximated by LV volume and arterial blood pressure (BP) obtained from the cardiac catheterization in previous basic and clinical studies [10–15]. We subsequently calculated these variables with an echocardiographic volume calculation and BP measurement by the Korotkoff technique using the manchette method, and this
123
J Artif Organs
modification was clinically applied to various acquired and congenital heart diseases [16–20]. Here, we focus on AVR with the 16-mm ATS mechanical valve, one of the smallest mechanical valves, and apply this modification to analysis of the postoperative LV performance. The purpose of this study was to demonstrate the validity of this valve implantation in patients with a very small aortic annulus, based on the concept of cardiac energetics analysis.
Table 1 Baseline characteristics of all patients Characteristics
n = 11
Sex (male, female)
0, 11
Age (median, years)
81.6 (58.3–89.1)
Body surface area (mean, m2)
1.33 ± 0.15
Etiology of aortic valve disease Aortic stenosis
7
Aortic stenosis with regurgitation
4
Bicuspid aortic valve
2
Comorbidities
Materials and methods
Ischemic heart disease, Previous PCI
3, 1
Other valvular lesion (mitral and/or tricuspid valve)
3
Patient population
Peripheral artery disease
2
From January 2005 to December 2010, a total of 146 consecutive patients (91 mechanical valves, 55 bioprosthetic valves) underwent AVR at Aso Iizuka Hospital. Of 91 patients who underwent AVR with a mechanical valve, 16 (all female) underwent implantation with the 16-mm ATS mechanical valve. Five patients were excluded from this study; two patients died within one year after AVR due to noncardiac cause, and all the other three patients were alive at the time of writing this report, who could not be analyzed the cardiac energetics due to their data deficits. Eleven patients were enrolled in this study. The patients’ baseline characteristics are summarized in Table 1. All patients’ preoperative condition was determined to be sufficient, and all underwent the elective operation. The clinical and operative records of enrolled patients were retrospectively reviewed, and the individual patients were not identified. This study was approved by our institutional committee on human research. Operative techniques and postoperative anticoagulant therapy A median sternotomy was performed in all patients, and standard cardiopulmonary bypass was established. The valve size was determined based on the aortic annulus diameter as measured with a sizer. A 16-mm ATS-Advanced Performance (AP) valve was used in seven patients, and a 16-mm ATS-AP360 valve was used in four patients. The mechanical valve was implanted at an intra-annular position (10 patients) or supra-annular position (1 patient). Valve implantation at the intra-annular position was the first-choice standard technique in our institution; only when aortic annulus is too small to allow for implantation at the intra-annular position, the prosthetic valve was implanted at the supra-annular position. All operations were conducted without aortic annular enlargement. Isolated AVR was performed in eight patients. Concomitant procedures were required in three patients; coronary artery bypass grafting in two patients, mitral
123
Chronic obstructive pulmonary disease
2
On-hemodialysis
1
NYHA functional class (mean) I, II, III, IV
2.3 ± 0.7 1, 6, 4, 0
Preoperative echocardiographic data Aortic valve area (cm2)
0.57 ± 0.21
Peak pressure gradient across the aortic valve (mmHg) LV ejection fraction (%)
98.9 ± 40.5
2
LV mass index (g/m )
64.7 ± 7.5 167.9 ± 36.7
Data are presented as the number of patients or as the mean ± SD or the median value (range) LV left ventricular, NYHA New York Heart Association, PCI percutaneous coronary intervention
annuloplasty for severe mitral regurgitation in one patient, tricuspid annuloplasty for severe tricuspid regurgitation in one patients, and pulmonary vein isolation for paroxysmal atrial fibrillation in one patient. Anticoagulant therapy was administered to all patients, and prothrombin time was targeted at an international normalized ratio of 2.0–3.0. Antiplatelet therapy was simultaneously administered in all patients. Definition of prosthesis-patient mismatch A reference effective orifice area (EOA) index was defined as a commercially available EOA normalized the body surface area (BSA), and a prosthesis-patient mismatch (PPM) was defined as the reference EOA index of 0.85 cm2/ m2 or less as described in previous papers [21, 22]. Hemodynamic evaluation by pressure gradient, ejection fraction, and LV mass All echocardiographic examinations were performed by skilled examiners with either Sonos 5500 (Philips
J Artif Organs
Electoronics, Andover, MA) or Vivid 7 (GE Medical System, Milwaukee, WI). All patients underwent transthoracic echocardiographic examinations before AVR, after AVR (approximately 1 month after surgery), and at a one-year follow-up (approximately one year after surgery). The data were obtained from two-dimensional M-mode measurement and Doppler echocardiographic measurement, and the peak pressure gradient across the aortic valve (peak PG), the LV ejection fraction (LVEF), and the LV mass were calculated. The peak PG was calculated by the Bernoulli formula from maximum velocity across the aortic valve in systole [23]. The LV end-systolic volume (LVESV) and LV end-diastolic volume (LVEDV) were calculated by the Teichholz method [24]. The LVEF was calculated as follows: LVEF = (1 – LVESV/ LVEDV) 9 100 (%) [25]. The LV mass was calculated by the Devereux formula [25], and the obtained value was normalized by the BSA to define the LV mass index (LVMI). Changes in these conventional hemodynamic variables were investigated at the three above-described time points.
cardiac function by this approximation method is 5.07 ± 2.03 mmHg/ml/m2, Ea is 3.01 ± 0.76 mmHg/ml/ m2, Ea/Ees is 0.66 ± 0.26, and SW/PVA is 75.8 ± 6.7 %, respectively [16]. Statistical analysis Continuous variables were expressed as the mean ± SD or median value and were compared by unpaired t tests. Repeated measures one-way analysis of variance (RMANOVA) was used for the variables at the three measured time points (before AVR, after AVR, and at a one-year follow-up) in all patients, and the Student–Newman–Keuls test was used as a post hoc test. A p value of \0.05 was considered to be statistically significant. GraphPad Prism 5.0 (GraphPad Software Inc., San Diego, CA) was used for all statistical analysis.
Results Follow-up after AVR
Cardiac energetics analysis with approximation method The cardiac energetics variables include Ees, Ea, Ea/Ees, and SW/PVA. Ees represents the load-independent index of contractility, and Ea represents the index of afterload. Ea/Ees represents ventriculoarterial coupling between the LV and the arterial system [7]. Ea/Ees and SW/PVA are the indices of ventricular efficiency [26]. The theoretical background and the validity of approximation method were particularly described in ‘‘Appendix’’. End-systolic elastance and Ea were calculated with the same approximation formula as previously reported [16– 20]: Ees = corrected mean BP/minimal LV volume and Ea = maximal LV pressure/(maximal LV volume – minimal LV volume). In this study, the LV volume was obtained from the echocardiographic data, and the arterial BP was measured by the Korotkoff technique using the manchette method. The maximal LV volume was defined as identical with the LVEDV, and the minimal LV volume was defined as identical with the LVESV. Each LV volume was normalized by the BSA. The maximal LV pressure was corrected by the peak PG; maximal LV pressure = arterial systolic BP ? peak PG. The corrected mean BP was calculated from the maximal LV pressure and the arterial diastolic BP; corrected mean BP = (maximal LV pressure ? 2 9 arterial diastolic BP)/3. Ea/Ees was the ratio of Ea to Ees. SW/PVA was calculated with the following theoretical formula: SW/PVA = 1/(1 ? 0.5 Ea/Ees) [26]. Changes in these cardiac energetic variables were investigated at the three above-described time points. As previously described, Ees of patients with normal
The mean follow-up period was 35.9 ± 17.5 months, and the longest follow-up period was 73.3 months. There were two late mortalities during the follow-up period. One patient died of progressive heart failure due to mitral regurgitation 12.2 months after AVR, and another patient died of a noncardiac cause 28.2 months after AVR. No aortic valve-related adverse events occurred during all enrolled patients’ follow-up period. Changes in conventional hemodynamic variables after AVR Conventional hemodynamic variables include peak PG, LVEF, and LVMI. Comparisons of these variables obtained from the echocardiographic data among the three time points are shown in Fig. 1a–c. The peak PG significantly decreased after AVR and at the one-year follow-up (from 98.9 ± 40.5 to 43.6 ± 15.6 and 38.9 ± 9.4 mmHg, p \ 0.0001, by RM-ANOVA). The LVEF hardly changed after AVR, but was significantly improved at the one-year follow-up (from 64.7 ± 7.5 to 64.0 ± 9.4 and 72.9 ± 7.6 %, p = 0.011, by RMANOVA). The LVMI also hardly changed after AVR, but significantly decreased at the one-year follow-up (from 167.9 ± 36.7 to 152.8 ± 44.3 and 126.2 ± 35.3 g/ m2, p = 0.004, by RM-ANOVA). The peak PG, LVEF, and LVMI were significantly improved at the one-year follow-up compared with those before AVR (p \ 0.001, p \ 0.05, and p \ 0.01, respectively, by the post hoc test).
123
J Artif Organs
B LVEF [%]
A Peak PG [mmHg]
C LVMI [g/m2] 300
90 150
250
80 ‡,
100
200
70
150
60 50
*
†,
100
*
50 50 0 Before AVR
After AVR
At 1-year follow-up
Before AVR
D Ees [mmHg/ml/m2] 10
After AVR
At 1-year follow-up
Before AVR
E Ea [mmHg/ml/m2]
After AVR
At 1-year follow-up
F Ea/Ees
G SW/PVA [%]
2.0
90
1.5
80
10 ‡,
70 5
1.0
‡
5
†
‡,
60
0.5 50 0
0
0 Before AVR
After AVR
At 1-year follow-up
Before AVR
After AVR
At 1-year follow-up
* p < 0.001, † p < 0.01, ‡ p < 0.05 vs. before AVR;
Before AVR
After AVR
At 1-year follow-up
Before AVR
After AVR
At 1-year follow-up
p < 0.05 vs. after AVR.
Fig. 1 Changes in conventional hemodynamic variables (a–c) and cardiac energetics variables (d–g) at the three time points (Before AVR, approximately one month after AVR [After AVR], and approximately one year after AVR [At one-year follow-up]). a The peak PG significantly decreased after AVR and at the one-year follow-up. b, c The LVEF (b) and the LVMI (c) hardly changed after AVR, but both were significantly improved at the one-year follow-up. d Ees transiently decreased after AVR and then recovered to the preAVR value at the one-year follow-up. e Ea significantly decreased in a stepwise manner. f, g Ea/Ees (f) and SW/PVA (g) were significantly
improved at the one-year follow-up compared with those before AVR. Closed circles and solid lines indicate the mean of all patients; bars indicate the standard deviation. The Student–Newman–Keuls test was used as a post hoc test. AVR aortic valve replacement, peak PG peak pressure gradient across the aortic valve, LVEF left ventricular ejection fraction, LVMI left ventricular mass index, Ees end-systolic elastance, Ea effective arterial elastance, Ea/Ees ventriculoarterial coupling, SW/PVA stroke work to pressure–volume area ratio
Cardiac energetics analysis after AVR
between Ea before AVR and that at the one-year follow-up (p \ 0.01, by the post hoc test). Ea/Ees and SW/PVA were significantly improved (Ea/Ees, from 1.1 ± 0.4 to 1.0 ± 0.4 and 0.7 ± 0.3, p = 0.020, by RM-ANOVA; SW/ PVA, from 66.3 ± 8.5 to 67.9 ± 8.3 and 75.6 ± 7.6 %, p = 0.011, by RM-ANOVA). These values were recovered to the normal level at the one-year follow-up. There was also a statistically significant difference between these values before AVR and at the one-year follow-up (p \ 0.05 for both, by the post hoc test). Further, comparison of these variables between the patients group with or without PPM at the one-year follow-up was shown in Table 3. There was no significant difference between the two groups.
Comparisons of the cardiac energetics variables among the three time points are shown in Fig. 1d–g. The measured parameters for calculation of Ees and Ea are presented in Table 2. Ees did not significantly change among the three time points (from 6.3 ± 3.0 to 5.2 ± 2.1 and 6.9 ± 2.3 mmHg/ml/m2, p = 0.15, by RM-ANOVA). Ees transiently decreased after AVR and then recovered to the pre-AVR value at the one-year follow-up. Ea significantly decreased in a stepwise manner (from 5.8 ± 1.1 to 4.6 ± 1.3 and 4.2 ± 1.2 mmHg/ml/m2, p = 0.005, by RMANOVA). There was a statistically significant difference
123
J Artif Organs Table 2 Measured parameters for calculation of cardiac energetics variables Parameters Heart rate (bpm)
Before AVR
After AVR
At one-year follow-up
68.8 ± 12.6
75.7 ± 13.4
63.6 ± 14.6
128.4 ± 26.1
121.4 ± 11.4
134.5 ± 34.8
Arterial diastolic BP (mmHg)
68.9 ± 9.1
64.5 ± 6.9
64.2 ± 16.4
Peak PG across the aortic valve (mmHg)
98.9 ± 40.5
Maximal LV pressure (mmHg)
227.3 ± 40.3
165.0 ± 15.7
173.5 ± 40.7
Corrected mean BP (mmHg)
121.7 ± 15.4
98.0 ± 6.3
100.6 ± 23.8
Maximal LV volume (ml/m2)
63.5 ± 16.9
61.4 ± 20.5
59.5 ± 14.8
Minimal LV volume (ml/m2)
23.3 ± 10.3
22.9 ± 12.8
16.7 ± 8.2
Arterial systolic BP (mmHg)
Table 3 Comparison of cardiac energetics variables and associated parameters between the patients group with or without PPM at the midterm follow-up Cardiac energetics variables and associated parameters Reference EOA index (cm2/m2)
With PPM (n = 3) 0.80 ± 0.06
Without PPM (n = 8) 0.95 ± 0.08*
Cardiac energetics variables
43.6 ± 15.6*
38.9 ± 9.4*
Ees (mmHg/ml/m2)
7.5 ± 2.2
6.7 ± 2.5
Ea (mmHg/ml/m2)
4.5 ± 0.2
4.1 ± 1.4
Ea/Ees SW/PVA (%)
The maximal LV pressure was corrected by the peak PG across the aortic valve; maximal LV pressure = peak PG ? arterial systolic BP. The corrected mean BP was calculated from the maximal LV pressure and the arterial diastolic BP; corrected mean BP = (maximal LV pressure ? 2 9 arterial diastolic BP)/3. The maximal LV volume and the minimal LV volume were defined as identical with the LV enddiastolic volume and the LV end-systolic volume calculated by echocardiography, respectively, and each LV volume was normalized by the body surface area AVR aortic valve replacement, BP blood pressure, PG pressure gradient, LV left ventricular * p \ 0.001 versus before AVR;
p \ 0.01 versus before AVR
0.7 ± 0.4 75.4 ± 8.8
Associated parameters Heart rate (bpm)
Data are presented as the mean ± SD
0.6 ± 0.1 76.0 ± 4.4
Arterial systolic BP (mmHg)
55.3 ± 7.1
66.8 ± 15.7
141.0 ± 24.9
132.1 ± 39.1
Arterial diastolic BP (mmHg)
66.3 ± 8.5
63.4 ± 19.0
Peak PG across the aortic valve (mmHg)
40.4 ± 9.2
38.4 ± 10.0
Maximal LV pressure (mmHg)
181.4 ± 27.2
170.5 ± 46.0
Corrected mean BP (mmHg)
104.7 ± 14.2
99.1 ± 27.2
Maximal LV volume (ml/m2)
55.4 ± 12.9
61.0 ± 16.0
2
Minimal LV volume (ml/m ) LV ejection fraction (%) LV mass index (g/m2)
15.1 ± 5.5
17.3 ± 9.3
73.4 ± 4.2
72.7 ± 8.7
113.4 ± 18.5
131.0 ± 39.9
Data are presented as the mean ± SD The reference EOA index was defined as a commercially available EOA normalized the body surface area, and a PPM was defined as a reference EOA index of 0.85 cm2/m2 or less BP blood pressure, Ees end-systolic elastance, Ea effective arterial elastance, Ea/Ees the ratio of Ea to Ees, SW/PVA the stroke work to pressure–volume area ratio, EOA effective orifice area, PPM prosthesis-patient mismatch, LV left ventricular * p \ 0.05 versus with PPM group
Discussion After AVR with the 16-mm ATS mechanical valve, the LV contractility (Ees) did not significantly change, and the afterload (Ea) was significantly reduced in a stepwise manner. The ventricular efficiency (Ea/Ees and SW/PVA) was also significantly improved. This tendency was verified approximately one year after AVR. AVR with the 16-mm ATS mechanical valve in patients with a very small aortic annulus was validated with respect to the significant improvement of LV performance at the postoperative midterm. Improvement in ventricular efficiency at midterm after AVR with 16-mm ATS mechanical valve In this study, the LV contractility transiently decreased after AVR compared with that before AVR and then recovered to the pre-AVR value at the one-year follow-up. As shown in Table 2, approximately one month after AVR, an abrupt decrease in LV pressure, which resulted from the
release of the aortic valve stenotic lesion, would bring about a simultaneous decrease in contractility. Subsequently, approximately one year after AVR, the LV contractility recovery was achieved due to reduction of minimal LV volume. The afterload reduction in a stepwise manner resulted from an initial decrease in LV pressure due to the release of the aortic valve stenotic lesion and the following reduction of minimal volume. Consequently, cooperation between contractility recovery and afterload reduction can contribute to the improvement in ventricular efficiency at the midterm follow-up, whereas this cooperation cannot be obtained in the short-term postoperative period. These results are similar to our previous paper which has described the LV performance in isolated AVR for aortic stenosis [16, 20]. A persistent and proper postoperative afterload reduction treatment is important until LV adaptation due to reverse remodeling is achieved. Thereafter, the improvement in ventricular efficiency could be verified at the postoperative midterm, as shown in Fig. 1f, g.
123
J Artif Organs
Significance of cardiac energetics analysis after AVR with 16-mm ATS mechanical valve So far, the absence of PPM, the cardiac function improvement, and the LV mass regression have been widely used to evaluate the effectiveness of AVR. The impact of PPM on a prognosis of patients who underwent AVR is still controversial [21, 22], but its effectiveness is always associated with its potential of PPM, especially when discussing AVR in patients with a very small aortic annulus. In this study, the peak PG at one year after AVR was 38.9 ± 9.4 mmHg, which was maintained until the most recent follow-up. This value was almost equivalent to that in previous reports [5, 6]. Of this study patients, three patients had the reference EOA index of less than 0.85 cm2/m2, in whom neither cardiac events nor LV functional impairment was found during the follow-up period. The LVEF and the LV mass can conveniently provide good practical informations. However, the LVEF, which represents the load-dependent index of contractility, does not explain the LV contractility and the afterload separately; the LV mass, which represents the index of LV hypertrophy, does not also associated with the concept of ventricular efficiency. On the other hand, the cardiac energetics analysis can provide additional practical informations over conventional hemodynamic variables; it can simultaneously explain the load-independent LV contractility and the afterload separately. The LVMI is available as a static hemodynamic index, whereas the ventricular efficiency (Ea/Ees and SW/PVA) can play a role as a dynamic hemodynamic index. Additionally, the cardiac energetics analysis can make it easy to understand the above-described process of contractility recovery and afterload reduction. These understandings are beneficial for postoperative optimal medical treatment (e.g., diagnosis of whether the cardiac functional impairment resulted from systolic dysfunction or afterload mismatch). The cardiac energetics analysis does not contradict the conventional understandings and has an additional role for a better understanding of the patients’ clinical conditions, coupling with conventional hemodynamic variables. In terms of this point, the cardiac energetics variables may serve as promising indices of the cardiac function. Contribution of the 16-mm ATS mechanical valve to simplification of operative procedures Aortic valve replacement with additional aortic annular enlargement and stentless valve implantation by the fullroot method to avoid PPM is associated with major invasiveness due to its complex manipulations, which can cause certain complications. The median age of enrolled patients was 81.6 years, and six patients were octogenarians.
123
Almost all of these patients had some associated comorbidities, as well as aortic valve disease, as shown in Table 1. In addition, almost all patients had not only aortic valve lesions, but also a severely calcified sinus of Valsalva and ascending aorta, which often made it difficult to conduct the annular enlargement. The 16-mm ATS mechanical valve implantation can simplify the operative procedure and minimize the operative invasiveness, which can lead to a decrease in the incidence of operative complications. Operative strategy for aortic valve lesions in our institution In our institution, AVR with a bioprosthetic valve has been performed as the first-choice standard technique for aged patients to avoid the major complications associated with anticoagulant therapy. No bleeding events were found in this enrolled patients, but aged patients have potential bleeding risks associated with anticoagulant therapy. Only when aortic annulus is too small to allow for implantation of the smallest bioprosthetic valve, we will choose the smallest mechanical valve. This study verified the satisfactory midterm LV performance after AVR with the 16-mm ATS mechanical valve. A 16-mm ATS mechanical valve is an effective prosthetic valve in patients with a very small aortic annulus, and the use of this valve should be considered in patients whose small aortic annulus cannot allow for the smallest bioprosthetic valve implantation. Study limitations This retrospective study has some inherent limitations. First, this study included a small group and heterogenous population. Patients who undergo AVR with a 16-mm mechanical valve constitute a rare and limited population, and some patients were required concomitant procedure. Second, the two types of 16-mm mechanical valve, ATSAP valve and ATS-AP360 valve, were used for AVR. ATS-AP360 valve is the next generation prosthesis to ATS-AP valve, whose shape of sewing cuff is modified and allows for valve implantation in patients with a smaller aortic annulus. Third, the LV volume was calculated by the Teichholz method. Simpson’s method is more suitable than the Teichholz method for LV volume calculation. Also, the LV pressure was not precisely corrected because the PG value was possibly overestimated. Fourth, the approximation of Ees and Ea was not as accurate as measurements obtained from a conductance catheter system. This approximation method has so far only been validated in the animal model where cardiac function is normal [10] and has several modifications as described in ‘‘Appendix’’. Last, the correlation between ventricular efficiency improvement and reverse remodeling achievement was not
J Artif Organs
elucidated due to a small group. However, we believe that these limitations are acceptable for cardiac energetics analysis and that these limitations do not detract from the validity of our conclusions. The future study subjected the larger group can elucidate the more remarkable significance of cardiac energetics analysis.
Conclusion The midterm LV performance after AVR with the 16-mm ATS mechanical valve was satisfactory. The validity of this valve implantation was elucidated based on the concept of cardiac energetics analysis. The cardiac energetics variables, coupling with the conventional hemodynamic variables, can contribute to a better understanding of the patients’ clinical conditions, and those may serve as promising indices of the cardiac function. Conflict of interest There is no conflict of interest or disclosure for any of the authors with any companies/organizations whose product/ services discussed in this manuscript.
Appendix Theoretical background The cardiac energetics variables include Ees, Ea, and Ea/ Ees and SW/PVA. Ees represents the load-independent index of contractility; Ea represents the index of afterload; and Ea/Ees and SW/PVA are the indices of ventricular efficiency. As particularly described in previous investigations, Ees is the slope of the end-systolic pressure–volume relation [8], and Ea is the ratio of end-systolic pressure to stroke volume [9]. Ea/Ees represents ventriculoarterial coupling between the LV and the arterial system [7]. SW represents the external mechanical work, and PVA represents the total mechanical energy generated by ventricular contraction. The ratio of SW to PVA can be understood as the energy efficiency. These variables are actually determined from the multiple LV pressure–volume loops with a conductance catheter system. Furthermore, SW/PVA can be theoretically predicted by Ees and Ea as follows: SW/ PVA = 1/(1 ? 0.5 Ea/Ees) [26]. Validity of approximated Ees and Ea We previously described the approximation methods of Ees and Ea as follows: approximated Ees = mean arterial pressure/minimal ventricular volume; approximated Ea = maximal ventricular pressure/(maximal ventricular volume – minimal ventricular volume) [10]. With this modification, the cardiac energetics variables can be easily
calculated.The important point is that end-systolic ventricular volume and end-diastolic ventricular volume according to the pressure–volume loop are not same as minimal ventricular volume and maximal ventricular volume, respectively. Normally, end-systolic ventricular volume is larger than minimal ventricular volume and end-diastolic ventricular volume is lower than maximal ventricular volume. Another important point is that endsystolic ventricular pressure is smaller than maximal ventricular pressure. In these points, the present approximated Ees and Ea are not precisely identical with Ees and Ea measured with a conductance catheter system. In particular, the approximated Ees is calculated not as the ratio of end-systolic pressure to end-systolic ventricular volume, but as the ratio of mean arterial blood pressure to minimal ventricular volume, and therefore, the volume intercept is not defined as zero [15]. The high correlations between Ees and the approximated Ees and between Ea and the approximated Ea were experimentally validated in the basic study using a canine right heart bypass preparation with a conductance catheter system [10]. This modification has the advantages that ventricular volume and blood pressure are measured with the cardiac catheterization, which enables the cardiac energetics analysis in various clinical situations [10–15]. Further modifying this modification in the recent study, the LV performance has been analyzed with the echocardiographic ventricular volume calculation and noninvasively measured blood pressure [16–20]. This modification can be the promising analysis method of ventricular efficiency.
References 1. Nicks R, Cartmill T, Bernstein L. Hypoplasia of the aortic root. The problem of aortic valve replacement. Thorax. 1970; 25:339–46. 2. S, Imai Y, Iida Y, Nakajima M, Tatsuno K. A new method for prosthetic valve replacement in congenital aortic stenosis associated with hypoplasia of the aortic valve ring. J Thorac Cardiovasc Surg. 1975;70:909–17. 3. Manouguian S, Seybold-Epting W. Patch enlargement of the aortic valve ring by extending the aortic incision into the anterior mitral leaflet. New operative technique. J Thorac Cardiovasc Surg. 1979;78:402–12. 4. Ennker IC, Albert A, Dalladaku F, Rosendahl U, Ennker J, Florath I. Midterm outcome after aortic root replacement with stentless porcine bioprostheses. Eur J Cardiothorac Surg. 2011;40:429–34. 5. Nakamura Y, Nakano K, Tagusari O, Kataoka G, Seike Y, Domoto S, Ito Y. An alternative option for elderly patients with a small aortic annulus: the 16 mm ATS valve. J Heart Valve Dis. 2009;18:691–7. 6. Kobayashi Y, Fukushima Y, Hayase T, Kojima K, Endo G. Clinical outcome of aortic valve replacement with 16-mm ATSadvanced performance valve for small aortic annulus. Ann Thorac Surg. 2010;89:1195–9.
123
J Artif Organs 7. Burkhoff D, Sagawa K. Ventricular efficiency predicted by an analytical model. Am J Physiol. 1986;250:R1021–7. 8. Suga H. Ventricular energetics. Physiol Rev. 1990;70:247–77. 9. Sunagawa K, Maughan WL, Burkhoff D, Sagawa K. Left ventricular interaction with arterial load studied in isolated canine ventricle. Am J Physiol. 1983;245:H773–80. 10. Tanoue Y, Sese A, Ueno Y, Joh K, Hijii T. Bidirectional Glenn procedure improves the mechanical efficiency of a total cavopulmonary connection in high-risk fontan candidates. Circulation. 2001;103:2176–80. 11. Tanoue Y, Ando H, Fukumura F, Umesue M, Uchida T, Taniguchi K, Tanaka J. Ventricular energetics in endoventricular circular patch plasty for dyskinetic anterior left ventricular aneurysm. Ann Thorac Surg. 2003;75:1205–9. 12. Tanoue Y, Sese A, Imoto Y, Joh K. Ventricular mechanics in the bidirectional glenn procedure and total cavopulmonary connection. Ann Thorac Surg. 2003;76:562–6. 13. Tanoue Y, Kado H, Maeda T, Shiokawa Y, Fusazaki N, Ishikawa S. Left ventricular performance of pulmonary atresia with intact ventricular septum after right heart bypass surgery. J Thorac Cardiovasc Surg. 2004;128:710–7. 14. Tanoue Y, Kado H, Shiokawa Y, Fusazaki N, Ishikawa S. Midterm ventricular performance after Norwood procedure with right ventricular-pulmonary artery conduit. Ann Thorac Surg. 2004;78:1965–71. 15. Tanoue Y, Kado H, Ushijima T, Tominaga R. Consequences of a hypertensive right ventricle on left ventricular performance of patients with pulmonary atresia and intact ventricular septum after right heart bypass surgery. Prog Pediatr Cardiol. 2010;29:43–8. 16. Tanoue Y, Maeda T, Oda S, Baba H, Oishi Y, Tokunaga S, Nakashima A, Tominaga R. Left ventricular performance in aortic valve replacement. Interact CardioVasc Thorac Surg. 2009;9:255–9. 17. Tanoue Y, Tomita Y, Morita S, Tominaga R. Ventricular energetics in aortic root replacement for annuloaortic ectasia with aortic regurgitation. Heart Vessels. 2009;24:41–5. 18. Imasaka KI, Tomita Y, Tanoue Y, Tominaga R, Tayama E, Onitsuka H, Ueda T. Early mitral valve surgery for chronic severe mitral regurgitation optimizes left ventricular performance and left ventricular mass regression. J Thorac Cardiovasc Surg. 2012;146:61–6.
123
19. Nagata H, Ihara K, Yamamura K, Tanoue Y, Shiokawa Y, Tominaga R, Hara T. Left ventricular efficiency after ligation of patent ductus arteriosus for premature infants. J Thorac Cardiovasc Surg. 2013;146:1353–8. 20. Tanoue Y, Oishi Y, Sonoda H, Nishida T, Nakashima A, Tominaga R. Left ventricular performance after aortic valve replacement in patients with low ejection fraction. J Artif Organs. 2013;15:444–50. 21. Jamieson WR, Ye J, Higgins J, Cheung A, Fradet GJ, Skarsgard P, Germann E, Chan F, Lichtenstein SV. Effect of prosthesispatient mismatch on long-term survival with aortic valve replacement: assessment to 15 years. Ann Thorac Surg. 2010;89:51–9. 22. Head SJ, Mokhles MM, Osnabrugge RL, Pibarot P, Mack MJ, Takkenberg JJ, Bogers AJ, Kappetein AP. The impact of prosthesis-patient mismatch on long-term survival after aortic valve replacement: a systematic review and meta-analysis of 34 observational studies comprising 27186 patients with 133141 patient-years. Eur Heart J. 2012;33:1518–29. 23. Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, Griffin BP, Iung B, Otto CM, Pellikka PA, Quin˜ones M. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. J Am Soc Echocardiogr. 2009;22:1–23. 24. Teichholz LE, Kreulen T, Herman MV, Gorlin R. Problems in echocardiographic volume determinations: echocardiographicangiographic correlations in the presence of absence of asynergy. Am J Cardiol. 1976;37:7–11. 25. Lang RM, Bierig M, Devereux RB, Flachskampf M, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18:1440–63. 26. Nozawa T, Yasumura Y, Futaki S, Tanaka N, Uenishi M, Suga H. Efficiency of energy transfer from pressure-volume area to external mechanical work increases with contractile state and decreases with afterload in the left ventricle of the anesthetized closed-chest dog. Circulation. 1988;77:1116–24.
