Development and testing of a transcatheter heart valve with reduced calcification potential.

Introduction: Patients from developing countries who require heart valve surgery are younger and have less access to open heart surgery than those from developed countries. Transcatheter heart valves (THVs) may be an alternative but are currently unsuitable for young patients because of their inadequate durability. We developed and tested a THV utilizing two new types of decellularized bovine pericardial leaflets in an ovine model. Methods: The two decellularized tissues [one with a very low dose (0.05%) of monomeric glutaraldehyde (GA) fixation and detoxification (DF) and the other without glutaraldehyde (DE)] were compared to an industry standard [Glycar-fixed with the standard dose (0.625%) of glutaraldehyde]. THVs were manufactured with the three tissue types and implanted in the pulmonary position of nine juvenile sheep for 180 days. Baseline and post-explantation evaluations were performed to determine the hemodynamic performance of the valves and their dynamic strength, structure, biological interaction, and calcification. Results: Heart failure occurred in one animal due to incompetence of its Glycar valve, and the animal was euthanized at 158 days. The gradients over the Glycar valves were higher at the explant than at the implant, but the DE and DF valves maintained normal hemodynamic performance throughout the study. The DF and DE tissues performed well during the mechanical testing of explanted leaflets. Glycar tissue developed thick pannus and calcification. Compared to Glycar, the DF tissue exhibited reduced pannus overgrowth and calcification and the DE tissue exhibited no pannus formation and calcification. All tissues were endothelialized adequately. There was a striking absence of host ingrowth in the DE tissue leaflets, yet these leaflets maintained integrity and mechanical function. Conclusion: In the juvenile sheep THV model, Glycar tissue developed significant pannus, calcification, and hemodynamic deterioration. Using a very low dose of monomeric GA to fix the decellularized bovine pericardium yielded less pannus formation, less calcification, and better hemodynamic function. We postulate that the limited pannus formation in the DF group results from GA. Bovine pericardium decellularized with our proprietary method resulted in inert tissue, which is a unique finding. These results justify further development and evaluation of the two decellularized tissue types in THVs for use in younger patients.

Transcatheter heart valve interventions for patients with rheumatic heart disease.

Rheumatic heart disease [RHD] is the most prevalent cause of valvular heart disease in the world, outstripping degenerative aortic stenosis numbers fourfold. Despite this, global resources are firmly aimed at improving the management of degenerative disease. Reasons remain complex and include lack of resources, expertise, and overall access to valve interventions in developing nations, where RHD is most prevalent. Is it time to consider less invasive alternatives to conventional valve surgery? Several anatomical and pathological differences exist between degenerative and rheumatic valves, including percutaneous valve landing zones. These are poorly documented and may require dedicated solutions when considering percutaneous intervention. Percutaneous balloon mitral valvuloplasty (PBMV) is the treatment of choice for severe mitral stenosis (MS) but is reserved for patients with suitable valve anatomy without significant mitral regurgitation (MR), the commonest lesion in RHD. Valvuloplasty also rarely offers a durable solution for patients with rheumatic aortic stenosis (AS) or aortic regurgitation (AR). MR and AR pose unique challenges to successful transcatheter valve implantation as landing zone calcification, so central in docking transcatheter aortic valves in degenerative AS, is often lacking. Surgery in young RHD patients requires mechanical prostheses for durability but morbidity and mortality from both thrombotic complications and bleeding on Warfarin remains excessively high. Also, redo surgery rates are high for progression of aortic valve disease in patients with prior mitral valve replacement (MVR). Transcatheter treatments may offer a solution to anticoagulation problems and address reoperation in patients with prior MVR or failing ventricles, but would have to be tailored to the rheumatic environment. The high prevalence of MR and AR, lack of calcification and other unique anatomical challenges remain. Improvements in tissue durability, the development of novel synthetic valve leaflet materials, dedicated delivery systems and docking stations or anchoring systems to securely land the transcatheter devices, would all require attention. We review the epidemiology of RHD and discuss anatomical differences between rheumatic valves and other pathologies with a view to transcatheter solutions. The shortcomings of current RHD management, including current transcatheter treatments, will be discussed and finally we look at future developments in the field.

Dynamic Left Ventricular Outflow Tract Obstruction Post-Transcatheter Aortic Valve Replacement.

We describe the first case of successful management of left ventricular outflow tract obstruction developing late after transcatheter aortic valve replacement with right ventricular apical pacing. The possible mechanisms of obstruction resolution are described. (Level of Difficulty: Advanced.).

A new over-the-wire percutaneous mitral balloon valvuloplasty technique.

OBJECTIVES: To develop and evaluate a new over-the-wire technique for mitral valvuloplasty that is both technically easier and less costly. BACKGROUND: Rheumatic heart disease (RHD) and resultant mitral stenosis (MS) carries a significant burden of disease worldwide. The prevalence is however concentrated in lower income countries where the current gold standard for percutaneous mitral valvuloplasty (PMBV)-the Inoue technique, is not always available due to cost and technical complexity. METHODS: The development of an over-the-wire technique involving a steerable catheter to aid crossing of the valve and a dedicated TAVI wire is described. The procedure evolved over the initial eight cases and the final standardized procedure was performed in 16 cases. Clinical, echocardiographic and procedural outcomes are described in 16 consecutive cases performed at a single center. RESULTS: The procedure was performed with 88% procedural success and only one technical failure during the development phase. 2/24 patients had moderate mitral regurgitation (MR) afterwards but one had unfavorable anatomy and the other had pre-procedural moderate MR. The average procedural duration was 66 min, which was shortened significantly over time. No procedural deaths or conversion to open surgery at 1 year. Procedural cost was 44% lower than the Inoue technique. CONCLUSION: We present favorable results of a new PMBV technique that is cheaper and technically easier in our opinion.

Extensive pulmonary metastases in young boy with primary cardiac angiosarcoma: a case report.

BACKGROUND: Malignant primary cardiac neoplasms are rare and primary cardiac angiosarcoma is the most common and aggressive subtype. It most commonly presents in middle-aged males and due to its non-specific clinical presentation, the diagnosis is often delayed until advanced disease is already present. Clinical presentation is determined by manifestations of local infiltration or metastatic disease and making an early diagnosis is extremely challenging. CASE SUMMARY: A 15-year-old previously healthy boy was admitted to the emergency department with a history of pathological weight loss and functional decline. The patient was found to have a left-sided pneumothorax as well as bilateral diffusely spread pulmonary nodules on plain chest radiograph. Computed tomography chest confirmed widespread pulmonary metastases and a right atrial filling defect. Echocardiography revealed a right atrial tumour and transvenous endomyocardial biopsy of the tumour was done under fluoroscopic and echocardiographic guidance. A diagnosis of primary cardiac angiosarcoma was made. The patient demised shortly after presentation. DISCUSSION: Primary cardiac angiosarcoma is rare and even more so in patients as young as the case described. The diagnostic process poses several challenges to the clinician, of which the obtaining of a histological sample is one. This case report demonstrates aspects both unique and typical of this rare disease. It also describes an effective option for obtaining tissue for a histological diagnosis in patients whose clinical condition may not allow biopsy under general anaesthesia.

Radial artery dilatation to improve access and lower complications during coronary angiography: the RADIAL trial.

AIMS: The aim of this study was to explore the use of prolonged occlusion flow-mediated dilatation (PO-FMD) to dilate the radial artery prior to cannulation to increase cannulation success, reduce puncture attempts and reduce access-site complications in transradial coronary angiography. METHODS AND RESULTS: A total of 1,156 patients undergoing transradial coronary angiography were randomised into PO-FMD and sham PO-FMD groups. PO-FMD was achieved by a 10-minute inflation of a blood pressure cuff on the arm to above systolic pressure, followed by deflation with resultant radial artery dilation. In the sham PO-FMD group the cuff was not inflated. Operators were blinded to the intervention. Five hundred and eighty (580) patients were randomised to the sham PO-FMD group and 576 to the PO-FMD group. Cannulation failure was reduced with PO-FMD, with cannulation failure rates of 2.7% in the PO-FMD group and 5.8% in the sham PO-FMD group (p=0.01).The number of puncture attempts was reduced with the use of PO-FMD, with a median of one attempt in the PO-FMD group and two in the sham PO-FMD group (p<0.001). Radial artery pulsation loss (RAPL) was reduced with PO-FMD, with 1.4% in the PO-FMD group and 3.8% in the sham PO-FMD group (p=0.02). CONCLUSIONS: PO-FMD reduces cannulation failure rates, decreases puncture attempts, and decreases RAPL during transradial coronary angiography.

The de Winter's pattern revisited: a case series.

BACKGROUND: The de Winter's electrocardiogram (ECG) pattern signifying proximal left anterior descending (LAD) artery occlusion was first described in 2008. The ECG changes were thought to be static and mechanisms for this were suggested. In addition, the optimal management of these patients was reported to be via a primary percutaneous coronary intervention (PCI) strategy. CASE SUMMARY: Case 1: A 48-year-old gentleman presented with a 2-h history of ischaemic chest pain with initial de Winter's pattern on ECG. This progressed to anterior ST-elevation myocardial infarction (STEMI) complicated by ventricular fibrillation. Emergency angiography revealed a mid-vessel LAD occlusion which was successfully reperfused. Case 2: A 34-year-old female presented with a 2-h history of ischaemic chest pain with initial ECG showing a de Winter's pattern. Due to concerns of performing PCI timeously, a pharmacoinvasive strategy of reperfusion was adopted with resolution of the de Winter's pattern. Urgent angiography revealed a proximal LAD lesion which was successfully stented. DISCUSSION: The two cases highlight that the de Winter's pattern may in fact not be static, but rather lie along the continuum of ischaemia and may evolve into STEMI. In addition, we provide further evidence that if primary PCI cannot be offered in a timeous manner, thrombolytic therapy may be considered in such patients. The de Winter's pattern remains a high-risk ECG pattern that requires early recognition and intervention.

Balloon Aortic Valvuloplasty Using a Non-Occlusive Balloon Catheter: First Animal Experience.

BACKGROUND: Transcatheter aortic valve implants (TAVI) have revolutionised the treatment of elderly patients requiring aortic valve replacement. These patients often do not tolerate balloon valvuloplasty well, and a valvuloplasty balloon that would allow a degree of continued cardiac output during expansion would be beneficial. We tested such a balloon and describe our results in the sheep model. METHODS AND RESULTS: We developed a non-occlusive balloon (NOB) catheter. An acute experiment was performed where the NOB was inflated in six sheep in the aortic valve position without any attempt to arrest cardiac output. Two inflations were performed per animal: the first for 30 s and the second for 2-3 min. Standard occlusive balloons were inflated in two animals under rapid ventricular pacing to serve as controls. Mean pressure gradient across the NOB was 9.7 ± 5 mmHg during the inflations and all animals remained hemodynamically stable during NOB inflations. CONCLUSIONS: The novel non-occlusive balloon catheter, which permitted uninterrupted cardiac output for a prolonged period without the need for pacing-induced temporary cessation of cardiac output, is both feasible and well tolerated in the acute sheep model.

Hybrid internal mammary to left anterior descending bypass and transaortic transcatheter aortic valve implantation: a new treatment option for patients with complex disease.

The case is described of a hybrid trans-aortic transcatheter aortic valve implantation and off-pump left internal mammary artery to left anterior descending artery bypass surgery in a man with a tight left main lesion and severe symptomatic aortic stenosis.

Non-ST elevation myocardial infarction (NSTEMI) in three hospital settings in South Africa: does geography influence management and outcome? A retrospective cohort study.

BACKGROUND: Guidelines advise early angiography in non-ST elevation myocardial infarction (NSTEMI) to ensure an optimal outcome. Resource limitations in secondary hospitals in the Western Cape dictate a local guideline to treat NSTEMIs medically with out-patient assessment for angiography, unless mandatory indications for early angiography occur. METHODS: A retrospective cohort study assessed NSTEMIs at Tygerberg Hospital (TBH), Karl Bremer Hospital (KBH) and Worcester Hospital (WH) over one year. Two cohorts were analysed, secondary hospitals (KBH and WH; SH) and secondary service within a tertiary hospital (TBH). Where differences were found, sub-analysis compared WH and KBH. RESULTS: TBH and SH were similar at baseline and in clinical presentation. Cases at TBH were more likely to receive in-patient angiography (94 vs 51%, p < 0.0001), and had a lower in-patient mortality rate (6 vs 23%, p = 0.0326). There was no difference between KBH and WH in sub-analysis. CONCLUSION: This study confirmed that the management and mortality of NSTEMIs in the public health sector in the Western Cape, South Africa is not influenced by geography, but rather by the level of service available in the hospital of first presentation.

First case of trans apical implantation of an aortic valve in a patient with dextrocardia.

We describe the clinical presentation and implantation procedure of the first transcatheter aortic valve implantation described in a patient with dextrocardia.

Transcatheter aortic valve replacement in a patient with an anomalous origin of the right coronary artery.

We describe the first case of implantation of a transcatheter aortic valve implantation (TAVI) in a patient with an anomalous origin of the right coronary artery, coursing in between the aorta and pulmonary truncus to the right. After assessment of the risk of compression of the anomalous origin of the right coronary artery from the left coronary sinus (ARCA), the procedure was performed without complication. A brief discussion of the pathophysiology of ARCA is provided and the implications for TAVI as well as our recommendations are offered.

Bilateral ostial coronary stenosis and rheumatic aortic valve stenosis.

A 49-year-old patient presented with angina pectoris and clinical findings of aortic valve stenosis and regurgitation. Rheumatic aortic valve stenosis and regurgitation was diagnosed on echocardiography. Coronary angiography findings showed severe calcification in the aorta root with right coronary ostial occlusion, and were suggestive of left main ostial stenosis and proximal main stem stenosis, which was confirmed on CT angiography. Curvilinear calcification of the aorta was present on CT angiography. The findings suggested syphilitic aortitis. Syphilis serology was positive (RPR titre 1/16). The angina was caused by severe coronary ostial disease likely due to syphilitic aortitis and exacerbated by the rheumatic aortic valve stenosis and regurgitation.