The Nordic Aortic Valve Intervention (NOTION) trial comparing transcatheter versus surgical valve implantation: study protocol for a randomised controlled trial

Background

Degenerative aortic valve (AV) stenosis is the most prevalent heart valve disease in the western world. Surgical aortic valve replacement (SAVR) has until recently been the standard of treatment for patients with severe AV stenosis. Whether transcatheter aortic valve implantation (TAVI) can be offered with improved safety and similar effectiveness in a population including low-risk patients has yet to be examined in a randomised setting.

Methods/Design

This randomised clinical trial will evaluate the benefits and risks of TAVI using the transarterial CoreValve System (Medtronic Inc., Minneapolis, MN, USA) (intervention group) compared with SAVR (control group) in patients with severe degenerative AV stenosis. Randomisation ratio is 1:1, enrolling a total of 280 patients aged 70 years or older without significant coronary artery disease and with a low, moderate, or high surgical risk profile. Trial outcomes include a primary composite outcome of myocardial infarction, stroke, or all-cause mortality within the first year after intervention (expected rates 5% for TAVI, 15% for SAVR). Exploratory safety outcomes include procedure complications, valve re-intervention, and cardiovascular death, as well as cardiac, cerebral, pulmonary, renal, and vascular complications. Exploratory efficacy outcomes include New York Heart Association functional status, quality of life, and valve prosthesis and cardiac performance. Enrolment began in December 2009, and 269 patients have been enrolled up to December 2012.

Discussion

The trial is designed to evaluate the performance of TAVI in comparison with SAVR. The trial results may influence the choice of treatment modality for patients with severe degenerative AV stenosis.

Trial registration

ClinicalTrials.gov: NCT01057173     

Transcatheter aortic valve replacement: design, clinical application, and future challenges

Transcatheter aortic valve replacement (TAVR) is a new technology that recently has been shown to improve survival and quality of life in patients with severe symptomatic aortic stenosis who are not surgical candidates. The development and design of transcatheter valves has been ongoing for the past 20 years, and TAVR has now been approved by the FDA as a treatment for aortic stenosis in patients who are not surgical candidates. In the United States, there are currently two transcatheter valves available: the Edwards Sapien Valve and the Medtronic CoreValve. While similar in some design elements, they also have characteristic differences that affect both the mechanism of delivery as well as performance in patients. This review aims to take a closer look at the development of this new technology, review the published clinical results, and look toward the future of transcatheter valve therapeutics and the challenges therein.     

Infective complications after transcatheter aortic valve implantation: results from a single centre

After its first introduction in 2002, transcatheter aortic valve implantation (TAVI) has continuously gained more foothold for the treatment of severe aortic stenosis and is nowadays a viable treatment option for inoperable patients or patients at high risk for conventional surgical aortic valve replacement. Although ideally carried out in a so-called hybrid room, incorporating both the strict hygiene and advanced life support possibilities of the operating theatre and the imaging and percutaneous arsenal of the catheterisation suite, in most centres TAVI is at present performed in the catheterisation laboratory. This may raise concern about an increased risk of infection, since there the criteria that are applied regarding disinfection and sterilisation are not as stringent as those of the operating theatre. Therefore, we retrospectively assessed the number of infective complications in patients undergoing TAVI in the catheterisation lab of our institution. Eleven out of 73 patients developed a postprocedural infection, one of which could be attributed to the procedure itself, being superinfection of a surgical groin cut-down. Our conclusion is that percutaneous aortic valve implantation in a catheterisation laboratory is not associated with an increased risk of infective complications.     

Management of a protruding right coronary artery stent during aortic valve replacement for aortic stenosis

ABSTRACT: We describe the successful management of a stent protruding from the right coronary ostium into the aortic root in the setting of aortic valve replacement for aortic stenosis. Due to advances in medical care more elderly patients present for aortic valve surgery after percutaneous coronary intervention. Therefore, with an aging population due to advances in medical care, more patients will present for aortic valve surgery after percutaneous coronary intervention. We suggest a degree of caution before valve deployment in transcatheter aortic valve intervention or during annular manipulation in patients undergoing traditional aortic valve replacement with coexisting patent proximal stents.     

Transcatheter closure of paravalvular leaks: state of the art

Paravalvular leak (PVL) is a serious complication after surgical valve replacement or after transcatheter aortic valve replacement. Approximately 1–5% of PVLs can lead to serious clinical consequences, including congestive heart failure and/or haemolytic anaemia. For years, surgical re-intervention has been considered the treatment of choice for symptomatic patients with PVLs. However, surgical re-intervention is associated with a high risk of morbidity and mortality. Transcatheter PVL (TPVL) closure is a less invasive alternative to surgical re-intervention. The safety and feasibility of TPVL closure has been confirmed in several registries and a meta-analysis.In this review, we discuss the clinical implications and diagnosis of PVLs, technical considerations for TPVL, execution of the procedure and assessment of the results.     

Undiagnosed hypertrophic obstructive cardiomyopathy during transcatheter aortic valve replacement: a case report

Background

Transcatheter aortic valve replacement is indicated for severe symptomatic aortic stenosis in patients who have a very high or prohibitive surgical risk as assessed pre-procedurally by the Society of Thoracic Surgery Risk Score, EuroSCORE (II), frailty testing, and other predictors. When combined with another left ventricular outflow tract obstruction, careful consideration must be taken prior to proceeding with transcatheter aortic valve replacement because an additional masked left ventricular outflow tract pathology can lead to challenging hemodynamics in the peri-deployment phase, as reported in this case.

Case presentation

A 56-year-old Caucasian man with multiple comorbidities and severe aortic stenosis underwent transcatheter aortic valve replacement under monitored anesthesia care. During the deployment phase, he developed dyspnea that progressed to pulmonary edema requiring emergent conversion to general anesthesia, orotracheal intubation, acute respiratory distress syndrome-type ventilation, and vasopressor medications. Intraoperative transesophageal echocardiography was performed and hypertrophic obstructive cardiomyopathy with systolic anterior motion of the mitral valve was discovered as an underlying pathology, undetected on preoperative imaging. After treatment with beta blockers, fluid resuscitation, and alpha-1 agonists, he stabilized and was eventually discharged from our hospital without any lasting sequelae.

Conclusions

Patients with aortic stenosis most often develop symmetric hypertrophy; however, a small subset has asymmetric septal hypertrophy leading to left ventricular outflow tract obstruction. In cases of severe aortic stenosis, however, evidence of left ventricular outflow tract obstruction via both symptoms and echocardiographic findings may be minimized due to extremely high afterload on the left ventricle. Diagnosing a left ventricular outflow tract obstruction as the cause of hemodynamic instability during transcatheter aortic valve replacement, in the absence of abnormal findings on echocardiogram preoperatively, requires a high index of clinical suspicion. The management of acute onset left ventricular outflow tract obstruction intraoperatively consists primarily of medical therapy, including rate control, adequate volume resuscitation, and avoidance of inotropes. With persistently elevated gradients, interventional treatments may be considered.

     

Isolated splenic metastasis from colorectal carcinoma in a high risk patient: a case report

Isolated splenic metastasis arising from a colorectal carcinoma is a rare finding. We report a case of 74-year-old man with a medical history of diabetes type II and paroxysmal atrial fibrillation, who underwent a right hemicolectomy for an adenocarcinoma of caecum in August 2004. In June 2007 the patient was diagnosed with high grade aortic valve stenosis as well as long segment stenosis of the first obtuse marginal branch of left coronary artery. He was suggested aortic valve replacement with coronary artery bypass grafting but he refused the surgery. In October 2007 the patient underwent alpha 18FDG - PET scanning, due to increasing values of CEA serum level, which showed a 5 cm big isolated hypermetabolic lesion in the spleen. Due to operative risk, splenectomy was refused by surgeons. The patient underwent a chemotherapy with capecitabine in total of 8 cycles before his CEA level began to rise and MSCT showed a progression in size of splenic metastasis. The patients condition was reevaluated by a team of experts and splenectomy was performed in September 2008. In May 2009 during the postoperative follow up, MSCT scanning revealed enlarged lymph nodes in celiac region and hepatic lesion suspicious of metastasis and the patient was admitted for further chemotherapy treatment. There is still no standardized treatment for this condition due to small number of cases reported in literature. Splenectomy followed by chemotherapy seems to be an optimal treatment but still no final conclusions can be made.     

Patient-specific modeling of biomechanical interaction in transcatheter aortic valve deployment

The objective of this study was to develop a patient-specific computational model to quantify the biomechanical interaction between the transcatheter aortic valve (TAV) stent and the stenotic aortic valve during TAV intervention. Finite element models of a patient-specific stenotic aortic valve were reconstructed from multi-slice computed tomography (MSCT) scans, and TAV stent deployment into the aortic root was simulated. Three initial aortic root geometries of this patient were analyzed: (a) aortic root geometry directly reconstructed from MSCT scans, (b) aortic root geometry at the rapid right ventricle pacing phase, and (c) aortic root geometry with surrounding myocardial tissue. The simulation results demonstrated that stress, strain, and contact forces of the aortic root model directly reconstructed from MSCT scans were significantly lower than those of the model at the rapid ventricular pacing phase. Moreover, the presence of surrounding myocardium slightly increased the mechanical responses. Peak stresses and strains were observed around the calcified regions in the leaflets, suggesting the calcified leaflets helped secure the stent in position. In addition, these elevated stresses induced during TAV stent deployment indicated a possibility of tissue tearing and breakdown of calcium deposits, which might lead to an increased risk of stroke. The potential of paravalvular leak and occlusion of coronary ostia can be evaluated from simulated post-deployment aortic root geometries. The developed computational models could be a valuable tool for pre-operative planning of TAV intervention and facilitate next generation TAV device design.     

C-Reactive protein reactions to glucose-insulin-potassium infusion and relations to infarct size in patients with acute coronary syndromes

Little is known about preoperative predictors of resource utilization in the treatment of high-risk patients with severe symptomatic aortic valve stenosis. We report results from the prospective, medical-economic “TAVI Calculation of Costs Trial”. In-hospital resource utilization was evaluated in 110 elderly patients (age ≥ 75 years) treated either with transfemoral (TF) or transapical (TA) transcatheter aortic valve implantation (TAVI, N = 83), or surgical aortic valve replacement (AVR, N = 27). Overall, 22 patient-specific baseline parameters were tested for within-group prediction of resource use. Baseline characteristics differed between groups and reflected the non-randomized, real-world allocation of treatment options. Overall procedural times were shortest for TAVI, intensive care unit (ICU) length of stay (LoS) was lowest for AVR. Length of total hospitalization since procedure (THsP) was lowest for TF-TAVI; 13.4 ± 11.4 days as compared to 15.7 ± 10.5 and 21.2 ± 15.4 days for AVR and TA-TAVI, respectively. For TAVI and AVR, EuroScore I remained the main predictor for prolonged THsP (p <0.01). Within the TAVI group, multivariate regression analyses showed that TA-TAVI was associated with a substantial increase in THsP (55 to 61 %, p <0.01). Additionally, preoperative aortic valve area (AVA) was identified as an independent predictor of prolonged THsP in TAVI patients, irrespective of risk scores (p <0.05). Our results demonstrate significant heterogeneity in patients baseline characteristics dependent on treatment and corresponding differences in resource utilization. Prolonged ThsP is not only predicted by risk scores but also by baseline AVA, which might be useful in stratifying TAVI patients. German Clinical Trial Register Nr. DRKS00000797     

A calcified polymeric valve for valve-in-valve applications

The prevalence of aortic valve stenosis (AS) is increasing in the aging society. More recently, novel treatments and devices for AS, especially transcatheter aortic valve replacement (TAVR) have significantly changed the therapeutic approach to this disease. Research and development related to TAVR require testing these devices in the calcified heart valves that closely mimic a native calcific valve. However, no animal model of AS has yet been available. Alternatively, animals with normal aortic valve that are currently used for TAVR experiments do not closely replicate the aortic valve pathology required for proper testing of these devices. To solve this limitation, for the first time, we developed a novel polymeric valve whose leaflets possess calcium hydroxyapatite inclusions immersed in them. This study reports the characteristics and feasibility of these valves. Two types of the polymeric valve, i.e., moderate and severe calcified AS models were developed and tested by deploying a transcatheter valve in those and measuring the related hemodynamics. The valves were tested in a heart flow simulator, and were studied using echocardiography. Our results showed high echogenicity of the polymeric valve, that was correlated to the severity of the calcification. Aortic valve area of the polymeric valves was measured, and the severity of stenosis was defined according to the clinical guidelines. Accordingly, we showed that these novel polymeric valves closely mimic AS, and can be a desired cost-saving solution for testing the performance of the transcatheter aortic valve systems in vitro.     

Surgical treatment of infective endocarditis with special reference to prosthetic valve endocarditis.

Patients with native valve endocarditis treated surgically between 1968 and 1978 (n = 15) and all patients presenting with prosthetic valve endocarditis during this period (n = 21) were followed up for at least four years. Five of the patients with native valve endocarditis required urgent early surgical intervention, of whom two died. The remaining 10 underwent valve replacement after a course of antibiotic treatment: all survived, though one required further valve replacement. The 21 patients with prosthetic valve endocarditis suffered 25 attacks. Nine were cured by medical treatment alone; two died before surgical intervention was possible; 11 required valve replacement, of whom three died; and two required valve replacement after a course of antibiotic treatment. The incidence of early prosthetic valve endocarditis--that occurring within two months of operation--was 0.67%, but that of late prosthetic valve endocarditis could not be determined. Medical treatment when started early should cure endocarditis in most patients, but vigilance should be maintained for the appearance of indications for surgery. When such indications exist surgery should not be delayed.     

High resolution three-dimensional strain mapping of bioprosthetic heart valves using digital image correlation

Transcatheter aortic valve replacement (TAVR) is a safe and effective treatment option for patients deemed at high and intermediate risk for surgical aortic valve replacement. Similar to surgical aortic valves (SAVs), transcatheter aortic valves (TAVs) undergo calcification and mechanical wear over time. However, to date, there have been limited publications on the long-term durability of TAV devices. To assess longevity and mechanical strength of TAVs in comparison to surgical bioprosthetic valves, three-dimensional deformation analysis and strain measurement of the leaflets become an inevitable part of the evaluation. The goal of this study was to measure and compare leaflet displacement and strain of two commonly used TAVs in a side-by-side comparison with a commonly used SAV using a high-resolution digital image correlation (DIC) system. 26-mm Edwards SAPIEN 3, 26-mm Medtronic CoreValve, and 25-mm Carpentier-Edwards PERIMOUNT Magna surgical bioprosthesis were examined in a custom-made valve testing apparatus. A time-varying, spatially uniform pressure was applied to the leaflets at different loading rates. GOM ARAMIS® software was used to map leaflet displacement and strain fields during loading and unloading. High displacement regions were found to be at the leaflet belly region of the three bioprosthetic valves. In addition, the frame of the surgical bioprosthesis was found to be remarkably flexible, in contrary to CoreValve and SAPIEN 3 in which the stent was nearly rigid under a similar loading condition. The experimental DIC measurements can be used to characterize the anisotropic materiel behavior of the bioprosthetic heart valve leaflets and validate heart valve computational simulations.     

颅底孔在多层CT三维重建中的测量研究

探讨颅底MSCT三维重建图像效果及主要孔的正常值,采用多层螺旋CT(MSCT),对200名正常成人(男100名,女100名)进行颅脑扫描,利用电子计算机三维重建程序立体地显示颅底外面的卵圆孔、棘孔、颈动脉管外口、破裂孔、茎乳孔、枕骨大孔,并观察其形态和测出其内径及其性差。     

The congenital bicuspid aortic valve can experience high-frequency unsteady shear stresses on its leaflet surface

The bicuspid aortic valve (BAV) is a common congenital malformation of the aortic valve (AV) affecting 1% to 2% of the population. The BAV is predisposed to early degenerative calcification of valve leaflets, and BAV patients constitute 50% of AV stenosis patients. Although evidence shows that genetic defects can play a role in calcification of the BAV leaflets, we hypothesize that drastic changes in the mechanical environment of the BAV elicit pathological responses from the valve and might be concurrently responsible for early calcification. An in vitro model of the BAV was constructed by surgically manipulating a native trileaflet porcine AV. The BAV valve model and a trileaflet AV (TAV) model were tested in an in vitro pulsatile flow loop mimicking physiological hemodynamics. Laser Doppler velocimetry was used to make measurements of fluid shear stresses on the leaflet of the valve models using previously established methodologies. Furthermore, particle image velocimetry was used to visualize the flow fields downstream of the valves and in the sinuses. In the BAV model, flow near the leaflets and fluid shear stresses on the leaflets were much more unsteady than for the TAV model, most likely due to the moderate stenosis in the BAV and the skewed forward flow jet that collided with the aorta wall. This additional unsteadiness occurred during mid- to late-systole and was composed of cycle-to-cycle magnitude variability as well as high-frequency fluctuations about the mean shear stress. It has been demonstrated that the BAV geometry can lead to unsteady shear stresses under physiological flow and pressure conditions. Such altered shear stresses could play a role in accelerated calcification in BAVs.     

Capacities of multidetector spiral computed tomography in the planning and postoperative examination of patients undergoing coronary artery bypass surgery

Multiple investigations show that multidetector spiral computed tomography (MSCT) bypass grafting becomes an alternative to invasive coronary angiography in detecting coronary graft stenoses and occlusions. The investigation retrospectively estimated the patency of aortocoronary and mammary coronary artery anastomoses by MSCT bypass grafting. Examinations were made in 85 (326 anastomoses) patients who had undergone aortocoronary and mammary coronary artery bypass surgery and had MSCT bypass grafting within 3 years after the surgery. In the first year following the surgery, 18 patients with graft stenotic changes, as evidenced by MSCT, underwent intervention coronary angiography, the sensitivity and specificity of which was 100%. The results of clinical and instrumental examinations were also compared with graft incompetence, as shown on MSCT that revealed that MSCT bypass grafting was the only noninvasive technique to evaluate early coronary graft closure both in the absence of clear signs of myocardial ischemia according to the data of exercise tests and in the presence of recurrent angina pectoris.     

64层螺旋CT对胸部创伤的诊断价值

目的:评价64层螺旋CT相对于CR片在胸部创伤诊断中的价值。方法:我院2006年1月～2008年3月收治81例胸部创伤,全部患者在伤后10min至5h进行了64层螺旋CT检查,其中58例在初次检查后12～38h内进行了CR或床旁CR检查,CT扫描采用GE LightSpeed 64层螺旋CT机,层厚0.625 mm,螺距为0.984:1。结果:81例中诊断肋骨骨折72例,肺挫裂伤65例,气胸36例,血胸53例,血气胸31例,锁骨骨折12例,肩胛骨骨折13例,皮下及纵隔积气18例,右横膈破裂2例。在同时进行过CR检查的患者中,非错位性及撕脱性肋骨、肋软骨骨折在CR上常显示不佳,而在64层螺旋CT多平面或三维重建图像上显示非常清晰。结论:64层螺旋CT多平面及三维重建对胸部创伤各种病变的检测明显优于x线平片,对临床急救计划的制定有重要的指导意义。     

Balloon dilatation of the aortic valve for inoperable aortic stenosis.

The place of balloon dilatation of the aortic valve in the treatment of calcific aortic stenosis is controversial. Thirty two patients (mean age 76) in whom valve replacement was contraindicated were followed up for three to 24 months (mean 8); 25 were in functional class III or IV according to the New York Heart Association''s classification. Major complications of the procedure occurred in four patients. Echocardiography and Doppler studies were performed before operation and before discharge in 28 patients, and the area of the valve was measured again six to 50 (mean 23) weeks after operation in 11 patients. The peak to peak aortic pressure gradient fell from a mean of 65 (SD 24) to 46 (20) mm Hg, but the area of the aortic valve, measured by Doppler echocardiography, in 18 patients showed a modest but significant increase, from 0.61 (0.16) to 0.74 (0.23) cm2. One month after dilatation, 29 patients were alive, of whom 17 had improved symptoms. Only two had lasting clinical benefit. Sixteen patients died, 12 of a cardiac cause. The estimated one year survival rate was 49%. Six patients underwent or required valve replacement because of persisting symptoms. In view of its limited long term efficacy balloon dilatation of the aortic valve should be used only for patients with severe symptoms whose life expectancy is limited by other disease or who are considered to be unsuitable for valve replacement. It may have a role in improving the condition of patients who present with cardiogenic shock or pulmonary oedema before valve replacement is undertaken.     

Location and functional characterization of the right atrioventricular pacemaker ring in the adult avian heart

Previous histological studies showed that in addition to a sinus node, an atrioventricular (AV) node, an AV bundle, left and right bundle branches, birds also possess a right AV‐Purkinje ring that is located in the atrial sheet of the right muscular AV‐valve along all its base length. The functionality of the AV‐Purkinje ring is unknown. In this work, we studied the topology of pacemaker myocytes in the atrial side of the isolated chicken spontaneously contracting right muscular AV‐valve using the method of microelectrode mapping of action potentials. We show that AV‐cells having the ability to show pacemaking reside in the right muscular AV‐valve. Pacemaker action potentials were exclusively recorded close to the base of the valve along its whole length from dorsal to the ventral attachment to the interventricular septum. These action potentials have much slower rate of depolarization, lower amplitude, and higher diastolic depolarization than action potentials of Purkinje (conducting) cells. We conclude the right AV‐valve has a ring bundle of pacemaker cells (but not Purkinje cells) in the adult chicken heart. J. Morphol. 277:363–369, 2016. © 2015 Wiley Periodicals, Inc.     

Experimental technique of measuring dynamic fluid shear stress on the aortic surface of the aortic valve leaflet

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. The exact cause and mechanism of the progression of AV calcification is unknown, although mechanical forces have been known to play a role. It is thus important to characterize the mechanical environment of the AV. In the current study, we establish a methodology of measuring shear stresses experienced by the aortic surface of the AV leaflets using an in vitro valve model and adapting the laser Doppler velocimetry (LDV) technique. The valve model was constructed from a fresh porcine aortic valve, which was trimmed and sutured onto a plastic stented ring, and inserted into an idealized three-lobed sinus acrylic chamber. Valve leaflet location was measured by obtaining the location of highest back-scattered LDV laser light intensity. The technique of performing LDV measurements near to biological surfaces as well as the leaflet locating technique was first validated in two phantom flow systems: (1) steady flow within a straight tube with AV leaflet adhered to the wall, and (2) steady flow within the actual valve model. Dynamic shear stresses were then obtained by applying the techniques on the valve model in a physiologic pulsatile flow loop. Results show that aortic surface shear stresses are low during early systole (<5 dyn/cm2) but elevated to its peak during mid to late systole at about 18-20 dyn/cm2. Low magnitude shear stress (<5 dyn/cm2) was observed during early diastole and dissipated to zero over the diastolic duration. Systolic shear stress was observed to elevate only with the formation of sinus vortex flow. The presented technique can also be used on other in vitro valve models such as congenitally geometrically malformed valves, or to investigate effects of hemodynamics on valve shear stress. Shear stress data can be used for further experiments investigating effects of fluid shear stress on valve biology, for conditioning tissue engineered AV, and to validate numerical simulations.     

老年瓣膜病患者瓣膜置换术术后死亡原因分析

目的:分析老年瓣膜病在瓣膜置换术后的死亡原因,为降低术后死亡率提供科学依据。方法:回顾分析我院以瓣膜置换术治疗的329例老年瓣膜病变患者的资料,对比分析生存患者和死亡患者之间的差异,总结瓣膜置换术后患者死亡的危险因素。结果:心脏瓣膜置换术后死亡率8.51%,单因素分析发现年龄、心功能分级、置换瓣膜数、LAD、LVEF、LVEDD、CPB时间、主动脉阻断时间、置换瓣膜数目与术后死亡有关联(P0.05),Logistic回归分析发现高龄、心功能差、LVEED、CPB为死亡独立危险因素(P0.05)。结论:高龄、心功能差、LVEED过度增大、CPB过长均是瓣膜置换术后的老年瓣膜病患者死亡的独立危险因素,建议临床在诊治中加以警惕。