Patient-specific computer modelling – its role in the planning of transcatheter aortic valve implantation

Transcatheter aortic valve implantation is increasingly used to treat patients with severe aortic stenosis who are at increased risk for surgical aortic valve replacement and is projected to be the preferred treatment modality. As patient selection and operator experience have improved, it is hypothesised that device-host interactions will play a more dominant role in outcome. This, in combination with the increasing number of valve types and sizes, confronts the physician with the dilemma to choose the valve that best fits the individual patient. This necessitates the availability of pre-procedural computer simulation that is based upon the integration of the patient-specific anatomy, the physical and (bio)mechanical properties of the valve and recipient anatomy derived from in-vitro experiments. The objective of this paper is to present such a model and illustrate its potential clinical utility via a few case studies.     

Early experience with the Venus p‑valve for percutaneous pulmonary valve implantation in native outflow tract

Introduction

The Venus p?valve (MedTech, Shanghai, China) is a self-expanding percutaneous heart valve designed to be implanted in a native patched right ventricle outflow tract. The worldwide clinical experience with this valve is just beginning and the results have so far been encouraging. We present our initial early experience implanting the Venus p?valve in the native right ventricle outflow tract of patients with Tetralogy of Fallot repaired with a transannular patch.

Methods

In 10 selected patients a procedure for percutaneous pulmonary valve implantation was performed using the Venus p?valve. The patients mean age was 32 years (13–57), mean weight 59.6?kg (40–80). All patients had Tetralogy of Fallot with moderate to severe pulmonary regurgitation and an indication for pulmonary valve replacement.

Results

The implantation procedure was successful in all the patients resulting in an immediately functional valve. No procedure-related complications were observed. Follow-up after 12 months (4–21) resulted in an improvement in NYHA class. There was a reduction of the mean right ventricle diastolic volume from 139?ml/m² (105–179) to 78?ml/m² (65–100) and improvement in the regurgitation fraction from 42% (29–58) to 1% (0–5), as seen on routine cardiac magnetic resonance 6 months after the implantation. No stent fractures have been observed so far.

Conclusion

Percutaneous pulmonary valve implantation with the Venus p?valve resulted in a safe and effective procedure. The valve has predictable and sustained functional competence, resulting in clinical improvement in the patients.

     

NT-proBNP and exercise capacity in adult patients with congenital heart disease and a prosthetic valve: a multicentre PROSTAVA study

Objectives

N-terminal B?type natriuretic peptide (NT-proBNP) is an important biomarker for the detection of heart failure. Adults with congenital heart disease (ACHD) and a prosthetic heart valve are at risk for heart failure. This study aimed to determine the value of NT-proBNP in ACHD patients with a prosthetic valve and investigate its relationship with cardiac function and exercise capacity.

Methods

In this multi-centre cross-sectional observational study, data regarding medical history, echocardiography, exercise testing (VO₂peak) and laboratory blood evaluation (including NT-proBNP) were collected in ACHD patients with a single prosthetic valve (either homografts, heterografts or mechanical valves).

Results

A total of 306 ACHD patients with pulmonary valve replacement (PVR, n = 139), aortic valve replacement (n = 141), mitral valve replacement (n = 21) or tricuspid valve replacement (n = 5) were investigated. The majority of patients (77?%) were in NYHA class I or II. Elevated NT-proBNP levels (cut-off ≥125 pg/ml) were found in 50?% of the patients, with the highest levels in patients with mitral valve replacements. In this study population, NT-proBNP levels were associated with gender (p = 0.029) and VO₂max (p < 0.001). In PVR patients, NT-proBNP levels were associated with lower VO₂peak, also after adjustment for age, gender and age at valve replacement in a multivariate model (p = 0.015).

Conclusions

In patients with ACHD and a prosthetic valve, elevated NT-proBNP levels are frequently observed despite preserved NYHA class. In PVR patients, a higher NT-proBNP level was associated with a lower VO₂peak. These results may be of importance in the ongoing discussion about the timing of valve replacement in patients with CHD.

     

Percutaneous closure of a left atrial appendage with relevant suture dehiscence

Atrial fibrillation is a widespread disease and highly relevant as it carries an extended risk for ischaemic stroke. Surgical closure of the left atrial appendage is routinely performed during open heart surgery in patients with atrial fibrillation with the aim of thromboembolic protection. In this report we present a successful percutaneous closure of a left atrial appendage, which showed clinically relevant suture dehiscence several years after surgical closure.     

Percutaneous closure of a patent foramen ovale after cryptogenic stroke

A patent foramen ovale is a common intracardiac finding that is located between the left and right atrium. It can cause right-to-left shunting and has a high prevalence in patients who suffer a cryptogenic stroke. Earlier trials did not show superiority of percutaneous patent foramen ovale closure with standard medical therapy over standard medical therapy alone in the treatment of cryptogenic stroke. Interestingly, several meta-analyses show positive results regarding closure, suggesting underpowering of the individual trials. Recently, two large prospective trials and one long-term follow-up study showed benefit of percutaneous closure over standard medical therapy in treatment of cryptogenic stroke. A larger right-to-left shunt or the presence of an atrial septal aneurysm were predictors for a recurrent event. Therefore, percutaneous patent foramen ovale closure after cryptogenic stroke should be recommended over antiplatelet therapy alone in patients younger than 55 years of age with a high-risk patent foramen ovale.     

Haemodynamic and functional consequences of the iatrogenic atrial septal defect following Mitraclip therapy

Percutaneous MitraClip placement for treatment of severe mitral regurgitation in high surgical risk patients is a commonly performed procedure and requires a transseptal puncture to reach the left atrium. The resulting iatrogenic atrial septal defect (iASD) is not routinely closed, yet the haemodynamic and functional consequences of a persisting defect are not fully understood. Despite positive effects such as acute left atrial pressure relief, persisting iASDs are associated with negative consequences, namely significant bidirectional shunting and subsequent worse clinical outcome. Percutaneous closure of the iASD may therefore be desirable in selected cases. In this review we discuss the available literature on this matter.     

Is there an alternative treatment for patients intolerant to antiplatelet therapy if percutaneous left atrial appendage closure is considered?

Introduction

Left atrial appendage (LAA) closure has become of major interest for patients with atrial fibrillation intolerant to oral anticoagulation therapy (OAC). Patients with a contraindication to both OAC and antiplatelet therapy are not eligible for percutaneous LAA closure. We aimed to find an alternative treatment for these specific patients.

Methods

From March 2014 until December 2015 five patients were referred for percutaneous LAA closure. Alternative treatment was necessary due to an absolute contraindication to OAC and antiplatelet therapy (n = 4) or after previous failed percutaneous device implantation (n = 1). A stand-alone full thoracoscopic closure of the LAA using the Atriclip PRO device (AtriCure Inc., Dayton, OH, USA) was performed under guidance of transoesophageal echocardiography (TEE). After three months all patients underwent a computed tomography scan. Mean follow-up was 7.2 months [range 4.5–9.8 months].

Results

All procedures were achieved without the occurrence of complications. Complete LAA closure was obtained in all patients without any residual flow confirmed by TEE. Postoperative computed tomography confirmed persisting adequate clip positioning with complete LAA closure and absence of intracardial thrombi. During follow-up no thromboembolic events occurred.

Conclusion

For atrial fibrillation patients with an absolute contraindication to OAC and antiplatelet therapy a stand-alone, minimally invasive thoracoscopic closure of the LAA is a safe and feasible alternative treatment. This might be a solution to avoid serious bleeding complications while eliminating the thromboembolic risk originating from the LAA in patients who are not eligible for percutaneous LAA closure.

     

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     

The last frontier: transcatheter devices for percutaneous or minimally invasive treatment of chronic heart failure

Heart failure has a high prevalence in the general population. Morbidity and mortality of heart failure patients remain high, despite improvements in drug therapy, implantable cardioverter-defibrillators and cardiac resynchronisation therapy. New transcatheter implantable devices have been developed to improve the treatment of heart failure. There has been a rapid development of minimally invasive or transcatheter devices used in the treatment of heart failure associated with aortic and mitral valve disease and these devices are being incorporated into routine clinical practice at a fast rate. Several other new transcatheter structural heart interventions for chronic heart failure aimed at a variety of pathophysiologic approaches are currently being developed. In this review, we focus on devices used in the treatment of chronic heart failure by means of left ventricular remodelling, left atrial pressure reduction, tricuspid regurgitation reduction and neuromodulation. The clinical evaluations of these devices are early-stage evaluations of initial feasibility and safety studies and additional clinical evidence needs to be gathered in appropriately designed clinical trials.     

Mitro-aortic pathology: a point of view for a fully transcatheter staged approach

Severe aortic valve stenosis (AVS) and mitral valve regurgitation (MVR) often coexist. Although a fully percutaneous treatment for the two conditions, by means of transcatheter aortic valve implantation (TAVI) followed by MitraClip, can be appealing in selected high-risk candidates, critical and strategical reasoning should be applied. In a 3-year period we have developed a single-centre experience of 14 patients who were managed with a staged percutaneous approach to treat severe AVS and MVR. The average interval from TAVI to MitraClip repair was 101 ± 12 days. Success for TAVI was 100% and 92.9% (13/14) for MitraClip. At late follow-up, 3 patients developed MVR 3+. Estimated 1?year survival was 66.5%. Freedom from 1?year endpoint (death, stroke, major bleeding, myocardial infarction, and cardiac re-hospitalisation) was 57.9%.In our view, a fully transcatheter approach for mitro-aortic pathology is feasible and should be performed only as a staged procedure in those patients that remain symptomatic, in spite of successful TAVI. It should be emphasised that although the periprocedural success rate is satisfactory, follow-up mortality and re-hospitalisation rates remain high, even at mid-term follow-up. This most probably results from the advanced clinical picture at time of referral for treatment.     

Transcatheter aortic valve replacement with the 34 mm Medtronic Evolut valve

Objectives

To report our experience with the recently introduced 34?mm Evolut transcatheter aortic valve replacement (TAVR) prosthesis.

Background

A larger TAVR prosthesis has become available for the treatment of aortic stenosis (AVS) in larger native aortic annuli (up to 30?mm). Outcomes with this new device are still unreported.

Results

The first 25 transfemoral TAVRs performed by our team with the self-expandable 34?mm Evolut are presented. The majority of patients were male (84%) with a mean age of 81.3?±?5.6 years, a median logistic euro-SCORE of 14.7 (5.4-61.0), and a computed tomography measured mean perimeter-derived aortic annulus diameter of 27.1?±?1.4?mm (min. 25.0–max. 31.2?mm). We implanted one 34?mm Evolut in all patients. Median operative time and radiation time were 68.5 and 12.4?min respectively. To optimise final valve position and haemodynamic performance, at least one complete re-sheathing and re-positioning of the same valve was reported in 33.2%. New permanent pacemaker implantation (PPMI) was necessary in 28.5%. At Receiver Operating Characteristic (ROC) analysis, a minimal diameter of the left ventricular outflow tract <21.9?mm was a significant predictor for PPMI (specificity 82%; sensitivity 83%; p?=?0.005; Area Under the Curve (AUC)?=?0.9). Length of stay in hospital was 9.2?±?5.8 days and no in-hospital death was reported. At discharge, grade 1?+?para-valvular regurgitation was present in 32%, and no regurgitation in the remaining patients. Device success and early safety were 100% and 92% respectively.

Conclusions

TAVR with the 34?mm Evolut prosthesis has shown satisfactory acute outcomes. Although results are consistent with those observed with smaller Evolut prostheses, a trend for a higher PPMI rate has been noticed and could derive from a higher oversizing rate.

     

Carcinoid heart disease: a guide for screening and timing of surgical intervention

The cardiac manifestations of a neuroendocrine tumour are referred to as carcinoid heart disease (CaHD) and are associated with a poor prognosis. Surgical intervention is the only proven therapeutic option and may prolong survival and quality of life. No consensus has been reached internationally with regard to screening for CaHD and the optimal timing for surgery. Although limited evidence is available on this matter, a trend towards early surgery and subsequent reduced mortality has been observed. In this review we provide an overview of the current understanding and propose a protocol to guide cardiologists in the screening for CaHD and the timing of referral to a specialised surgical centre.     

Three dimensional rotational angiography for assessment of coronary arteries during melody valve implantation: introducing a technique that may improve outcomes

Background

Adverse events from Melody valve implantation may be catastrophic. To date a role for three dimensional rotational angiography of the aortic root (3DRAA) during Melody valve implantation has not been established.

Objectives

To describe the role of 3DRAA in the assessment of Melody valve candidacy and to demonstrate that it may improve outcomes.

Methods

All patients who underwent cardiac catheterisation for Melody valve implantation and 3DRAA between August 2013 and February 2015 were reviewed.

Results

31 patients had 3DRAA with balloon sizing. Ten were deemed not Melody candidates (5 coronary compression, 2 aortic root distortion with cusp flattening, 2 RVOT was too large, and 1 had complex branch stenosis and a short landing zone). Of the 21 patients who were Melody candidates, 12 had conduits, 6 prosthetic valves and 3 native RVOTs. In patients with conduits, the technique of stenting the conduit prior to dilation was used after measuring the distance between the conduit and the coronary arteries on 3DRAA. In the Melody patients, we had 100% procedural success and no serious adverse events (coronary compression, tears, stent fracture or endocarditis).

Conclusion

As a tool for case selection, 3DRAA may facilitate higher procedural success and decreased risk of serious adverse events. Furthermore, 3D rotational angiography allows stenting of the conduit prior to dilation, which may prevent tears and possibly endocarditis.

     

二尖瓣成形术与二尖瓣生物瓣置换术治疗风湿性二尖瓣重度关闭不全的效果比较

目的:探讨二尖瓣成形术(Mitral valve plasty,MVP)与二尖瓣生物瓣置换术(Mitral valve replacement,MVR)治疗风湿性二尖瓣重度关闭的临床疗效和安全性。方法:选择我院2014年1月至2019年1月收治的因风湿性二尖瓣重度关闭而行二尖瓣成形术或二尖瓣生物瓣置换术的患者60例,其中二尖瓣成形术组(MVP组)27例,二尖瓣生物瓣置换术组(MVR组)33例。比较两组患者的围手术期各项指标,治疗前后的心功能指标(左心室射血分数,左心房内径、左心室收缩末期内径、左心室舒张末期内径)及二尖瓣反流情况以及术后并发症的发生情况。结果:(1)MVP组患者的手术时间、体外循环时间均明显长于MVR组(P0.05);而术中出血量、呼吸机使用时间、住院时间MVP组均显著低于MVR组(P0.05);(2)术后,MVP组的LVEF和LVEDD水平高于MVR组,而LAD和LVESD水平则低于MVR组(P 0.05);(3)出院前及末次随访时,MVP组二尖瓣反流发生率与MVR组相比差异均无统计学意义(P0.05)。(4)MVP组患者的术后并发症发生率低于MVR组(P 0.05)。结论:二尖瓣成形术治疗风湿性二尖瓣重度关闭的临床疗效和安全性优于二尖瓣生物瓣置换术,但术者需严格掌控MVP的手术适应症。     

Potential new mechanisms of pro-arrhythmia in arrhythmogenic cardiomyopathy: focus on calcium sensitive pathways

Arrhythmogenic cardiomyopathy, or its most well-known subform arrhythmogenic right ventricular cardiomyopathy (ARVC), is a cardiac disease mainly characterised by a gradual replacement of the myocardial mass by fibrous and fatty tissue, leading to dilatation of the ventricular wall, arrhythmias and progression towards heart failure. ARVC is commonly regarded as a disease of the intercalated disk in which mutations in desmosomal proteins are an important causative factor. Interestingly, the Dutch founder mutation PLN R14Del has been identified to play an additional, and major, role in ARVC patients within the Netherlands. This is remarkable since the phospholamban (PLN) protein plays a leading role in regulation of the sarcoplasmic reticulum calcium load rather than in the establishment of intercellular integrity. In this review we outline the intracellular cardiac calcium dynamics and relate pathophysiological signalling, induced by disturbed calcium handling, with activation of calmodulin dependent kinase II (CaMKII) and calcineurin A (CnA). We postulate a thus far unrecognised role for Ca²⁺ sensitive signalling proteins in maladaptive remodelling of the macromolecular protein complex that forms the intercalated disk, during pro-arrhythmic remodelling of the heart.     

Left atrial appendage closure: outcomes and challenges

Whereas the left atrial appendage plays a rather minor role under physiological circumstances, it gains an importance in patients with atrial fibrillation. Compelling evidence has revealed that the left atrial appendage is implicated as the source of thrombus in the vast majority of strokes in atrial fibrillation. Oral anticoagulation remains the standard of care for stroke prevention in atrial fibrillation; nevertheless, this treatment has several limitations and is often contraindicated, particularly in the elderly population in whom the risk of stroke is high. Therefore, occluding the left atrial appendage is a logical approach to prevent thrombus formation and subsequent cardioembolic events in these patients. We present a review of clinical outcomes of patients with atrial fibrillation undergoing left atrial appendage closure and the challenges faced in this field.     

The effect of aortic valve replacement on quality of life in symptomatic patients with severe aortic stenosis

Background

Although symptomatic patients with severe aortic stenosis have a high disease burden and guidelines recommend aortic valve replacement, many are treated conservatively. This study describes to what extent quality of life is changed by aortic valve replacement relative to conservative treatment.

Methods

This observational study followed 132 symptomatic patients with severe aortic stenosis who were subjected to an SF-36v2TM Health Survey.

Results

At baseline 84 patients were treated conservatively, 48 were referred for aortic valve replacement. In the conservatively treated group 15 patients died during a mean follow-up of 18 months (Kaplan-Meier survival was 85 % and 72 % at one and 2 years respectively) and 22 patients crossed over to the surgical group. Of the resulting 70 patients in the surgical group 3 patients died during a mean follow-up of 11 months (survival 95 % at 1 year). Physical functioning, vitality and general health improved significantly 1 year after aortic valve replacement. In conservatively treated patients physical quality of life deteriorated over time while general health, vitality and social functioning showed a declining trend. Mental health remained stable in both groups.

Conclusions

Aortic valve replacement improves physical quality of life, general health and vitality in patients with symptomatic severe aortic stenosis. Besides having a low life expectancy, conservatively treated patients experience deterioration of physical quality of life. Health surveys such as the SF-36v2TM can be valuable tools in monitoring the burden of disease for an individual patient and offer additional help in treatment decisions.     

Neueste technologische Entwicklungen für die Analyse von zirkulierender Tumor-DNA

The analysis of circulating tumor DNA (ctDNA) and circulating tumor cells, often known as liquid biopsy, is a rapidly developing field of medical research. Although it has taken decades since the discovery of cell-free DNA for it to be recognized as a suitable biomarker, the clinical benefit of ctDNA with regard to monitoring therapy response, the identification of resistance mechanisms, and novel emerging actionable targets, in addition to the detection of minimal residual disease, has recently been proven in numerous studies.Owing to the great variability of ctDNA in the circulation, together with the high degree of fragmentation, ctDNA is a challenging analyte. However, in recent years technological advances have contributed to a variety of routine applications of ctDNA analysis becoming a reality, given that a number of additional regulatory hurdles can be overcome.     

Benchmarking the use of blood products in cardiac surgery to stimulate awareness of transfusion behaviour

Introduction

Cardiac operations account for a large proportion of the blood transfusions given each year, leading to high costs and an increased risk to patient safety. Therefore, it is important to explore initiatives to reduce transfusion rates. This study aims to provide a benchmark for transfusion practice by inter-hospital comparison of transfusion rates, blood product use and costs related to patients undergoing coronary artery bypass grafting (CABG), valve surgery or combined CABG and valve surgery.

Methods

Between 2010 and 2013, patients from four Dutch hospitals undergoing CABG, valve surgery or combined CABG and valve surgery (n = 11,150) were included by means of a retrospective longitudinal study design.

Results

In CABG surgery the transfusion rate ranged between 43 and 54%, in valve surgery between 54 and 67%, and in combined CABG and valve surgery between 80 and 88%. With the exception of one hospital, the trend in transfusion rate showed a significant decrease over time for all procedures. Hospitals differed significantly in the units of blood products given to each patient, and in the use of specific transfused combinations of blood products, such as red blood cells (RBCs) and a combination of RBCs, fresh frozen plasma (FFP) and platelets.

Conclusion

This study indicates that benchmarking blood product usage stimulates awareness of transfusion behaviour, which may lead to better patient safety and lower costs. Further studies are warranted to improve awareness of transfusion behaviour and increase the standardisation of transfusion practice in cardiac surgery.

     

Genetics of autosomal recessive intellectual disability

In the last few years, next-generation sequencing has led to enormous progress in deciphering monogenic forms of intellectual disability. Autosomal dominant intellectual disability (ADID) and X chromosomal intellectual disability (XLID) have been the focus of research. Apart from metabolic disorders, autosomal recessive intellectual disability (ARID) is still behind, probably because it is more heterogeneous and less prevalent in industrial populations. The prevalence of ARID in a cohort of affected children of an outbred population is estimated to be about 10%, with an upward tendency in still unclarified cases. The risk for ARID in children of first cousins or closer is a magnitude higher than for children of unrelated parents. Taken together, it seems that children of related parents are at a 2 to 3 times higher risk for ID. There are no prevalent ARID genes, pathways, or protein complexes and the functions of the affected proteins are very diverse and limited not only to neurological aspects. Thus, in a regular case, there is no reasoning for picking a few genes for a first diagnostic step, and a genetic diagnosis of ID in general, and ARID specifically, is better made using large panels or exome sequencing. In addition, in the last few months, evidence has been growing that many ARID genes are pleiotropic and that the resulting phenotypes may have a broad spectrum. For an exhaustive deciphering of the genetics of ARID, we suggest research at the level of single genes rather than large meta-analyses.