Post-Discharge Antithrombotic Therapy Following Transcatheter Aortic Valve Implantation in Australian Patients.

BACKGROUND: Guidelines recommend antithrombotic therapy for patients following transcatheter aortic valve implantation (TAVI) to reduce the risk of ischaemic events and bioprosthetic valve thrombosis. OBJECTIVE: To describe antithrombotic dispensing within 30 days of discharge for Australian patients receiving TAVI. METHODS: We performed a state-wide retrospective cohort study using linked hospital and medicines dispensing data from January 2013 to December 2018 for all patients receiving TAVI in New South Wales, Australia. We identified patients dispensed oral anticoagulants (vitamin K antagonists [warfarin], direct oral anticoagulants [DOACs]) or clopidogrel within 30 days of discharge. We examined demographic and clinical predictors of antithrombotic dispensing. RESULTS: Our cohort comprised 1,217 patients who underwent TAVI; median age was 84 years and 707 (58.1%) were male. Of these, 808 patients (66.4%) had an antithrombotic dispensed within 30 days of hospital discharge. One-third (33.7%) of these patients were dispensed an anticoagulant (16.1% warfarin; 17.6% DOACs) and two-thirds (66.3%) were dispensed clopidogrel. Patients undergoing TAVI were more likely to be dispensed an antithrombotic medicine within 30-days of hospital discharge if they had been dispensed antithrombotic medicines (RR 1.07; 95% CI 1.03-1.11) or angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers (RR 1.04; 95% CI 1.00-1.07) in the 6 months prior to admission. Patients with a history of haemorrhage were less likely to be dispensed an antithrombotic medicine within 30 days of hospital discharge (RR 0.93; 95% CI 0.89-0.98). CONCLUSIONS: We observed gaps in best evidence pharmacotherapy for patients post-TAVI, with almost one third of patients not receiving antithrombotic medicines post-discharge. Further research is needed to quantify the impact of emerging clinical guidelines recommending single antiplatelet therapy, on adherence to best-practice care.

Adult and Paediatric Cardiac Intervention in Timor-Leste: Disease Burden, Demographics and Clinical Outcomes.

BACKGROUND: The East Timor Hearts Fund (ETHF) is a charitable organisation of Australian cardiologists providing outreach screening in Timor-Leste. For patients requiring intervention, ETHF arranges logistics, procedures, and postoperative care. The aim of this project is to evaluate outcomes of patients requiring intervention. METHODS: The ETHF database of all patients was utilised to identify patients with disease warranting surgical or percutaneous intervention. Both patients who underwent intervention and those who did not proceed to intervention were included in this study. Patients who had intervention arranged by other organisations but have then had follow-up with ETHF were also included. Overall demographics and pre and postoperative factors were assessed, with sub-group analysis of adult and paediatric patients to identify any differences in care. RESULTS: Of 221 patients requiring intervention, 101 patients underwent intervention, receiving 22 different operations or procedures. Patients were predominantly young (median age 17.5 years) and female (64.7%), with rheumatic heart disease (63.8%). Twenty-four (24) (33.3%) women aged 15-45 years old with cardiac disease warranting intervention were documented as pregnant or breastfeeding at time of clinic assessment. Of patients who did not proceed to intervention, adults were more likely to be lost to follow-up (42.4% vs 18.5%) while paediatric patients were more likely to experience progression of disease (18.5% vs 7.5%, p=0.005). Median waitlist time was 5 months, with no significant difference between adults and children, correlating with a preoperative mortality rate of 5.4%. For patients who underwent intervention, post-procedure mortality was extremely low (0.9%) and attendance of at least one post-procedure review was excellent (99.0%). Eleven (11) (10.9%) patients have required repeat intervention, with no difference in rates between adult and paediatric patients. Length of follow-up extends up to 20 years for some patients. CONCLUSION: The Timor-Leste interventional cohort was predominantly a young female population with rheumatic and congenital cardiac disease. There were also high rates of pregnancy amongst female patients with severe cardiac disease. Delayed access to intervention may result in preoperative adverse events and mortality, and is a key target for improvement. Patients who undergo intervention have very low post-procedural mortality, good adherence to early medical follow-up and good long-term outcomes.

Valve-in-Ring Transcatheter Heart Valve for Severe Tricuspid Regurgitation.

We report the case of a man with recurrent decompensated right-sided heart failure secondary to severe tricuspid regurgitation after tricuspid annuloplasty. He was unfit for repeat surgical intervention and thus was considered for a valve-in-ring transcatheter heart valve. We detail the procedural complexities encountered and our approach to overcoming them. (Level of Difficulty: Advanced.).

A missense mutation in kynurenine aminotransferase-1 in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) are the most extensively used animal model for genetic hypertension, increased stroke damage, and insulin resistance syndromes; however, the identification of target genes has proved difficult. SHR show elevated sympathetic nerve activity, and stimulation of the central blood pressure control centers with glutamate or nicotine results in exaggerated blood pressure responses, effects that appear to be genetically determined. Kynurenic acid, a competitive glutamate antagonist and a non-competitive nicotinic antagonist, can be synthesized in the brain by the enzyme kynurenine aminotransferase-1 (KAT-1). We have previously shown that KAT-1 activity is significantly reduced in SHR compared with normotensive Wistar Kyoto rats (WKY). Here we show that KAT-1 contains a missense mutation, E61G, in all the strains of SHR examined but not in any of the WKY or outbred strains. Previous studies on F2 rats from a cross of stroke-prone SHR and WKY have shown a suggestive level of linkage between elevated blood pressure and the KAT-1 locus on chromosome 3. In addition, the mutant enzyme expressed in Escherichia coli displays altered kinetics. This mutation may explain the enhanced sensitivity to glutamate and nicotine seen in SHR that may be related to an underlying mechanism of hypertension and increased sensitivity to stroke.