Development and validation of implantable sensors for monitoring function of prosthetic heart valves:<Emphasis Type="Italic">in vitro</Emphasis> studies

The development of a ‘smart’ heart valve prosthesis, with the intrinsic ability to monitor thrombus formation, mechanical failure and local haemodynamics and to relay this information externally, would be of significant help to clinicians. The first step towards such a valve is development of the sensors and examination of whether sensor output provides predictive information on function. Custom-made piezo-electric sensors were mounted onto the housing of mechanical valves with various layers of simulated thrombus and bioprosthetic valves with normal and stiffened leaflets. Sensor output was examined using joint time-frequency analysis. Sensors were able to detect leaflet opening and closing with high fidelity for all types of valve. The frequency content of the closing sounds for the mechanical valves contained several peaks between 100 Hz and 10 kHz, whereas closing sounds for the bioprosthetic valve contained energy in a lower frequency range (<1 kHz). A frequency peak of 47±15 Hz was seen for the normal bioprosthetic valve; this peak increased to 115±12 Hz for the valve with visibly stiffened leaflets. Total low-frequency (80–3500 Hz) energy content diminished predictably with increasing levels of thrombus for the mechanical valves. Lastly, closing sound intensity correlated well with closing pressure dynamics (dp/dt) (y=190x−443; r=0.90), indicating that the sensors also provide information on haemodynamics. These studies provide initial evidence regarding the use of embedded sensors to detect prosthetic valve function. Efforts to encapsulate these sensors with telemetry into a custom valve are currently underway.     

机械瓣心音频谱分析与基于改进LDB算法的识别

听诊是通过听取心脏所发出的声音来帮助诊断各种心脏疾病的一种有效手段。鉴于目前机械瓣的使用非常普遍,研究简单有效的机械瓣病变判别方法对于临床诊断来讲具有很大的意义。针对五种不同的机械瓣心音进行的分析表明,运用频谱仅能鉴别瓣周漏这一种机械瓣病变。虽然直接利用信号的时频成分进行机械瓣心音分类是可能的,但识别率只有84.0%。利用改进的局部最优基(LDB)算法来提取特征对机械瓣心音分类有着非常大的帮助,识别率达到了97.3%。与原始的LDB算法相比,实验表明改进后的LDB算法对提高识别率和降低计算复杂性都有着明显的优势。     

Incidence and outcomes of infective endocarditis after transcatheter aortic valve implantation versus surgical aortic valve replacement

ObjectivesTranscatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement (AVR) in aortic stenosis (AS). Infective endocarditis (IE) in patients with prosthetic heart valves is associated with significant morbidity and mortality. Data on the incidence, risk factors, and outcomes of IE after TAVI are conflicting. We evaluated these issues in patients with percutaneous TAVI vs. isolated surgical AVR (SAVR) at a nationwide level.MethodsBased on the administrative hospital discharge database, the study collected information for all patients with aortic stenosis treated with AVR in France between 2010 and 2018.ResultsA total of 47 553 patients undergoing TAVI and 60 253 patients undergoing isolated SAVR were identified. During a mean follow-up of 2.0 years (median (25th to 75th percentile) 1.2 (0.1–3.4) years), the incidence rates of IE were 1.89 (95% confidence interval (CI) 1.78–2.00) and 1.40 (95% CI 1.34–1.46) events per 100 person-years in unmatched TAVI and SAVR patients, respectively. In 32 582 propensity-matched patients (16 291 with TAVI and 16 291 with SAVR), risk of IE was not different in patients treated with TAVI vs. SAVR (incidence rates of IE 1.86 (95% CI 1.70–2.04) %/year vs 1.71 (95% CI 1.58–1.85) %/year respectively, relative risk (RR) 1.09, 95% CI 0.96–1.23). In these matched patients, total mortality was higher in TAVI patients with IE (43.0% 95% CI 37.3–49.3) than in SAVR patients with IE (32.8% 95% CI 28.6–37.3; RR 1.32, 95% CI 1.08–1.60).DiscussionIn a nationwide cohort of patients with AS, treatment with TAVI was associated with a risk of IE similar to that following SAVR. Mortality was higher for patients with IE following TAVI than for those with IE following SAVR.     

Effect of glutaraldehyde preservation on immunogenic,physicomechanical, and functional parameters of artificial aortic heart valves

Bulletin of Experimental Biology and Medicine -     

A modular mock circulation for hydromechanical studies on valves, stenoses, vascular grafts and cardiac assist devices.

P6vices for hydrodynamic simulation are required in a variety of studies such as device evaluation, cardiovascular modeling and for student training. Most studies today use different, incompatible circuits, which must be redesigned for every new application. To obtain a universal apparatus, a unitized system with standard connectors was developed. Three types of connectors were selected: 1" flange connectors, 1/2" tubing connectors and Luer-connectors with a 2 mm lumen. The complete system consists of reservoirs, throttles, valve holders, adapters for Doppler ultrasound probes, and converters to link these basic diameters. The apparatus can be driven by membrane, centrifugal and geared pumps. The system has successfully been used in echocardiographic studies of stenosis and valvular insufficiency, for pulse propagation in vascular grafts, and to test the hydraulic performance of cardiac assist devices. Flow rates between 0.1 and 30 l/min and pressure gradients up to 250 mmHg were achieved. In practical use, the system can be adapted to suit various investigations, with minimal expense. Standardization of the parts and connectors results in simple documentation and good reproducibility.     

Current status of left ventricular assist devices: the role in bridge to heart transplantation and future perspectives

Increasing numbers of patients with end-stage heart failure are awaiting heart transplantation worldwide. Left ventricular assist systems have been applied to these patients with increasing frequency and support duration. This situation calls for more reliably applied long-term support devices and is also stimulating the investigation of destination therapy or bridge to recovery use of the device. This is particularly relevant in countries where organ shortages are crucial. However, reports in this area are still limited, and there exist several problems to be solved before wider application of these strategies is possible in clinical practice. We review currently available devices with special reference to their respective roles and limitations quoting our own experiences over the past several years, and discuss future perspectives of ventricular assist devices.     

Comparison of spectral techniques for computer-assisted classification of spectra of heart sounds in patients with porcine bioprosthetic valves

The diagnositic performance of two spectral techniques (the fast Fourier transform, FFT, and autoregressive modelling, ARM) combined with four windowing functions (rectangular, Hanning, Hamming, and sine-cosine) and two classifiers (Bayes and nearest neighbour) to detect valvular degeneration was evaluated in a group of 95 patients. Forth-seven patients had a porcine bioprosthetic valve inserted in the aortic position and 48 patients had a porcine bioprosthetic valve inserted in the mitral position. Among the aortic valves, 24 were normal and 23 were degenerated whereas among the mitral valves, 19 were normal and 29 were degenerated. The aortic and mitral valves were analysed separately. For each type of valve, 21 features were extracted from the spectra of the valve closure sounds to train and test the performance of four pattern recognition systems by using the leave-one-out method. The discriminant properties of all feature combinations between two and five among the 21 features selected were evaluated. Results show that the FFT combined to the nearest neighbour classifier provided the best performances: 87 per cent of correct classifications (CCs) for aortic valves when using the Hanning or the Hamming window and 94 per cent of CCs for mitral valves when using the rectangular window. The best performances obtained with the ARM were 81 per cent of CCs for the aortic valves (nearest neighbour classifier and the Hanning or the Hamming window) and 92 per cent of CCs for the mitral valves (nearest neighbour classifier and the Hamming window or the Bayes classifier and the Hanning or the Hamming window).     

Mechanism for cavitation of monoleaflet and bileaflet valves in an artificial heart

It is possible that mechanical heart valves mounted in an artificial heart close much faster than those used for clinical valve replacement, resulting in the formation of cavitation bubbles. In this study, the mechanism for mechanical heart cavitation was investigated using the Medtronic Hall monoleaflet valve and the Sorin Bicarbon bileaflet valve mounted at the mitral position in an electrohydraulic total artificial heart. The valve-closing velocity was measured with a charge-coupled device (CCD) laser displacement sensor, and images of mechanical heart valve cavitation were recorded using a high-speed video camera. The valve-closing velocity of the Sorin Bicarbon bileaflet valve was lower than that of the Medtronic Hall monoleaflet valve. Most of the cavitation bubbles generated by the monoleaflet valve were observed near the valve stop; with the Sorin Bicarbon bileaflet valve, cavitation bubbles were concentrated along the leaflet tip. The cavitation density increased as the valve-closing velocity and the valve stop area increased. These results strongly indicate that squeeze flow holds the key to cavitation in the mechanical heart valve. From the perspective of squeeze flow, bileaflet valves with a low valve-closing velocity and a small valve stop area may cause less blood cell damage than monoleaflet valves.     

Mechanical circulatory support devices for bridge to heart transplantation, bridge to recovery, or destination therapy

Both the ventricular assist device (VAD) and the total artificial heart (TAH) have been effective in supporting circulation of end-stage cardiac patients and in bridging to heart transplantation. However, because of a shortage of donor hearts and age limitations, destination therapy with the completely implantable VAD has also been started. The totally implantable TAH in the United States is in the final stage of development and will go into preclinical trials in 2004. In Japan, heart transplantation has been re-instituted since last year, but because of shortages of donor hearts the waiting time prior to transplantation is fairly long. To date, six heart transplantations have been carried out, of which four have been bridged transplantations, using extracorporeal or implantable VADs. With the extracorporeal VADs, patients cannot be discharge home, which increases the hospital expenses. With the implantable VADs such as Novacor and HeartMate imported from the USA, patients can be discharged home, but major threats with these devices are thromboembolic, complications and infection. These devices are also fairly large, being designed for 80-kg patients, and are thus difficult to implant in patients of 50 to 60 kg, including women. Because of these limitations, there is a strong clinical demand for a compact, high-performance, implantable, permanent-use VAD. This paper addresses the current status of the artificial heart research and development program at the Tokyo Medical and Dental University, which was started in May 1999.     

心脏瓣膜假体植入和外科消融迷宫手术治疗瓣膜病合并心房颤动

文题释义：人工瓣膜置换或瓣环植入：由于二尖瓣成形术具有保留完善左心室结构和功能、减少血栓形成等优点,许多指南都推荐瓣膜成形作为二尖瓣病变的首选术式,而人工瓣环植入是瓣环成形的重要组成部分。但对于瓣叶及瓣下结构已存在严重病变的患者,瓣膜成形效果可能不佳,应行瓣膜置换。由于人工机械瓣的长期抗凝及血栓、出血等并发症,生物瓣存在耐久度问题;人工瓣膜选择是一个复杂的过程,必须平衡患者特征和材料的特定因素综合决定。 迷宫手术：通过切开和缝合形成一系列瘢痕来阻断心房颤动的信号传播。最初的手术方式常导致左心房功能障碍及起搏器植入高发生率,经过了两次换代,迷宫Ⅲ手术已成为心房颤动外科治疗的金标准。然而迷宫Ⅲ手术的复杂性和高技术难度阻止了其进一步推广。迷宫Ⅳ手术于2002年推出,射频消融与冷冻消融取代了原先的切开缝合,使得迷宫手术的受欢迎程度明显增加。背景：二尖瓣疾病患者二尖瓣置换与二尖瓣瓣环成形术后的心房颤动发生率较高,迷宫手术是心房颤动外科治疗的金标准,而人工瓣膜与瓣环对迷宫手术的影响不明确。 目的：评价瓣膜性房颤外科消融迷宫术后窦性心律-左心房收缩功能的变化规律,以及瓣膜置换或瓣环植入是否影响窦性心律-左心房收缩功能的恢复。 方法：纳入2013年10月至2017年10月中国人民解放军北部战区总医院收治的324例二尖瓣病变伴随持续性或长期持续性心房颤动患者,接受迷宫手术后均进行人工瓣膜置换或人工瓣环植入治疗。分别于出院时,术后1,3,6,12,24个月进行心电图和超声心动图随访。应用多因素Cox回归模型分析左心房收缩力恢复的预测因素。试验已通过中国人民解放军北部战区总医院(原沈阳军区总医院)伦理委员会批准。结果与结论：①2例患者(0.6%)在围术期死亡,其余322例患者均获得2年随访,随访期间无人工材料相关不良事件发生;②患者术后左心房收缩力恢复率逐步升高,至术后1年,左心房收缩力与窦性心律共存的一致性较好(Kappa系数≥0.75,P < 0.05),术后2年时窦性心律和左心房收缩力恢复率分别为86.6%和85.1%;③Cox多元回归分析显示,较长术前心房颤动时间、较大术前左心房内径、术后3个月左心房收缩力缺失和冷冻消融术式是迷宫术后中晚期(>3个月)窦性心律和左心房收缩力恢复的共同预测因素(P < 0.05),较长术前心房颤动持续时间、较大术前左心房内径、切开与缝合术式是左心房收缩力中晚期恢复的预测因素(P < 0.05),瓣膜置换或瓣环植入、材料类型及假体型号不是心房颤动和力中晚期恢复的影响因素(P > 0.05);④ROC曲线分析显示,术前心房颤动时间与术前左心房内径对左心房收缩力恢复的最佳预测临界值分别为36.5个月(敏感度90.5%,特异性93.7%)和60.5 mm(敏感度93.8%,特异性85.0%);⑤结果表明外科消融迷宫术后左心房收缩力恢复是一个动态提高的过程,早期左心房收缩力恢复有利于维持稳定的窦性心律,术前心房颤动持续时间延长、左心房内径增大及冷冻消融能量方式对外科消融迷迷宫手术存在不利影响,瓣环成形或瓣膜置换不会影响外科消融迷宫手术疗效。ORCID: 0000-0002-9632-7651(马超) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

New evidence for a critical role of elastin in calcification of native heart valves: immunohistochemical and ultrastructural study with literature review

Perrotta I, Russo E, Camastra C, Filice G, Di Mizio G, Colosimo F, Ricci P, Tripepi S, Amorosi A, Triumbari F & Donato G
(2011) Histopathology 59 , 504–513 New evidence for a critical role of elastin in calcification of native heart valves: immunohistochemical and ultrastructural study with literature review Aims: Calcific aortic stenosis is a progressive disease characterized by massive fibrosis andmineralization of the valve leaflets. The aim of this study was to determine whether the onset of native calcific aortic stenosis is associated primarily with matrix remodelling events, and particularly with elastin degradation. Methods and results: The immunohistochemical expression profile of matrix degradating enzymes and tenascin‐C was investigated in both healthy and native calcified aortic valves. Collagen and elastic tissue were studied by light microscopy and electron microscopy. Immunophenotypic analysis of inflammatory cells was carried out by using monoclonal antibodies to macrophages, T and B lymphocytes. Immunoreactivity for tenascin‐C and matrix metalloproteinase‐12 (MMP‐12) was associated with areas of dense mineralization, which were characterized by fibrosis, fragmentation and calcification of elastic fibres a positive reaction was also found around small islands of calcification. MMP‐11 was not detected in the diseased valves. Osteopontin and osteonectin were also found at sites of mineralization. All calcified valves examined showed inflammatory cell infiltration. Conclusions: Our results demonstrate the direct involvement of MMP‐12 in native aortic valve stenosis. MMP‐mediated degradation of elastic fibres might contribute actively to valve mineralization by inducing calcium deposition onto fragmented elastin.     

Morphology and morphogenesis of implanted valve-containing prostheses of the pulmonary trunk for surgical correction of complex congenital heart diseases

Morphology and morphogenesis of implanted valve-containing pulmonary trunk prostheses have been experimentally examined. It has been shown that 30 months after the operation there is total encapsulation of the graft and formation of the pseudointima layered with regenerated endothelium. In a xenograft sutured into the graft lumen, ultrastructural destructive changes develop gradually, however, the obturative function of graft has been preserved. All these facts allow us to recommend this type of graft for clinical use.     

Good design practice for medical devices and equipment,Part I: a review of current literature

Changes to the medical device regulations within the past few years have forced medical device manufacturers to take an integrated approach to design and validation in order to ensure that their products are reliable and fit for purpose. Good design practice encourages fitness for purpose within commercial reality. This paper contains a review of the current literature that is relevant to good design practice. The results show that there is inadequate guidance regarding the integration of validation with design. Thus, there is a need for good design practice to include 'design for validation' which is aimed at designing medical devices to make them easier and more economic to validate. Research has been carried out at the Cambridge Engineering Design Centre in order to develop an approach that provides guidance in order to help designers achieve integrated design, development and validation. This will be reported in part II of this paper.     

Validation of a cardiac monitor for measuring heart rate variability in adult female pigs: accuracy, artefacts and editing

Autonomic regulation of cardiac activity during stress has not been clearly defined in farm animals. In part, this is due to the limited availability of affordable ambulatory cardiac monitors capable of accurately monitoring and storing large amounts of data that meet the criteria necessary for heart rate variability analysis. Our objectives were to measure the accuracy of a 24-h Polar RR monitor using gold standard ECG, to examine and categorise any occurring anomalies and to ascertain their impact on the outcome of heart rate variability analysis. Five 1-year-old female pigs (gilts) were socially isolated from their pen mates and cardiac activity was simultaneously measured using two systems, a 24-h Polar RR Recorder and a Telemetric ECG system. The Polar data were manually assessed both against and in isolation of the ECG data to identify anomalous beats, which were then assigned to one of five identified error categories. The anomalies in the Polar data were corrected and statistical comparisons were performed among the three data sets to evaluate the effects of anomalies on heart rate variability analysis. Bland-Altman analysis was used to measure the level of agreement among the ECG, Uncorrected Polar and Corrected Polar data. No anomalies or ectopies were found in the ECG data but 46 anomalies (0.81% of total interbeat intervals [IBI]) were found in the Polar Uncorrected data. Manual identification and editing procedures reduced this error to 0.018%. Most mean heart rate and IBI parameters were unaffected by error (P>.05). Standard deviation (S.D.) and root mean square of successive differences (RMSSD) were 45% and 50% higher when anomalies were present in the data. Artefacts affected the magnitude of the frequency domain indices and overestimated total and parasympathetic activity and underestimated sympathetic activity. The mean difference between ECG and Uncorrected Polar data was 1.36 ms (limits of agreement -69.03 to 71.74 ms). This was greatly improved to 0.36 ms (limits of agreement -5.37 to 6.10 ms) after editing. Overall, even a small proportion of error biased the outcome of heart rate variability analysis. This bias was greatly reduced by correcting the anomalous beats. Bland-Altman analysis demonstrated that when there was error present in the Polar data, it could not be used interchangeably with the ECG data. However, if there were no anomalies present in the data or if they were classified and corrected using the approach in this study, then the two systems could be used interchangeably.     

Simple,noninvasive system for measuring the heart rate of avian embryos and hatchlings by means of a piezoelectric film

Using a flexible piezoelectric film, the authors developed a simple system to determine noninvasively the heart rate of chicken embryos and hatchlings. The film was piezoelectric polyvinylidene fluoride (PVDF), which is sensitive enough to detect cardiogenic ballistic movements of the egg (ballistocardiogram (BCG)) and precordial movements of the hatchling attributable to cardiac contractions (apexcardiogram (ACG)). The BCG could be detected, during the second half of incubation, by placing the egg on the PVDF film on a soft substrate. The detected signal was found to be a measure of movement velocity. The ACG could be measured when the hatchling's chest wall made contact with the PVDF film installed in a box in which the hatchling was confined. The heart rate was counted from the lag time of autocorrelation calculated for a certain time segment (e.g. 2s) of the BCG and ACG recordings.     

The effect of surgical approach in total knee replacement on outcomes. An analysis of 875,166 elective operations from the National Joint Registry for England,Wales, Northern Ireland and the Isle of Man

BackgroundTotal knee replacement (TKR) is clinically and cost-effective. The surgical approach employed influences the outcome, however there is little generalisable and robust evidence to guide practice. We compared outcomes between the common primary TKR surgical approaches.Methods875,166 primary TKRs captured in the National Joint Registry, linked to hospital inpatient, mortality and patient reported outcome measures (PROMs) data, with up to 15.75 years follow-up were analysed. There were 10 surgical approach groups: medial parapatellar, midvastus, subvastus, lateral parapatellar, ‘other’ and their minimally invasive versions. Survival methods were used to compare revision rates and 45-day mortality. Groups were compared using Cox proportional hazards regression and Flexible Parametric Survival Modelling (FPM). Confounders included age at surgery, sex, risk group (indications additional to osteoarthritis), American Society of Anesthesiologists grade, TKR fixation, year of primary, body mass index, and for mortality, deprivation and Charlson comorbidity subgroups. PROMs were analysed with regression modelling or non-parametric methods.ResultsThe conventional midvastus approach was associated with lower revision rates (Hazard Rate Ratio (HRR) 0.80 (95% CI 0.71–0.91) P = 0.001) and the lateral parapatellar with higher revision rates (HRR 1.35 (95% CI 1.12–1.63) P = 0.002) compared to the conventional medial parapatellar approach. Mortality rates were similar between approaches. PROMs showed statistically significant, but not clinically important, differences.ConclusionsThere is little difference in PROMs between the various surgical approaches in TKR with all resulting in good outcomes. However, the conventional midvastus approach (used in 3% of cases) was associated with a 20% reduced risk of revision surgery compared to the most commonly used knee approach (the conventional medial parapatellar: used in 91.9% of cases). This data supports the use of the midvastus approach and thus surgeons should consider utilising this approach more frequently. Minimally invasive approaches did not appear to convey any clinical advantage in this study over conventional approaches for primary TKR.     

BMP4 is required in the anterior heart field and its derivatives for endocardial cushion remodeling, outflow tract septation, and semilunar valve development

The endocardial cushions play a critical role in septation of the four-chambered mammalian heart and in the formation of the valve leaflets that control blood flow through the heart. Within the outflow tract (OFT), both cardiac neural crest and endocardial-derived mesenchymal cells contribute to the endocardial cushions. Bone morphogenetic protein 4 (BMP4) is required for endocardial cushion development and for normal septation of the OFT. In the present study, we show that anterior heart field (AHF)-derived myocardium is an essential source of BMP4 required for normal endocardial cushion expansion and remodeling. Loss of BMP4 from the AHF in mice results in an insufficient number of cells in the developing OFT endocardial cushions, defective cushion remodeling, ventricular septal defects, persistent truncus arteriosus, and abnormal semilunar valve formation.     

A methodological comparison of the Porges algorithm,fast Fourier transform,and autoregressive spectral analysis for the estimation of heart rate variability in 5‐month‐old infants

Little empirical evidence exists on the comparability of heart rate variability (HRV) quantification methods commonly used in infants. The aim was to compare three methods of HRV estimation: (1) fast Fourier transform (FFT), (2) autoregressive (AR), and (3) the Porges methods. HRV was estimated in 63 healthy 5‐month‐old infants. HRV parameters were strongly correlated across methods (.92–.99) but yielded significantly different mean HRV estimates (Porges method > FFT > AR). There was no systematic bias over the whole range of values between the two spectral approaches, while differences between the Porges method and the spectral estimates were systematically greater for larger values. Additional comparative studies are needed to explore the between‐method agreement across a range of physiological conditions.