Early Intervention in Asymptomatic Aortic Stenosis: What Are We Waiting For?

Aortic stenosis (AS) contributes to significant cardiovascular morbidity and mortality worldwide, and the natural history from symptoms to ventricular decompensation, heart failure, and death has been well documented. For more than 2 decades, technologies including imaging and biomarkers have shown a promising ability to detect myocardial damage associated with AS before symptoms arise. Current treatment guidelines rely heavily on symptoms or ventricular decompensation as triggers for aortic valve intervention. There is increasing appreciation of the relationship between myocardial damage due to AS before the emergence of symptoms, and a number of published randomised trials suggest a benefit to early intervention in asymptomatic AS, with additional trials actively enrolling. Future treatment paradigms may incorporate early detection of ventricular damage by noninvasive new technologies as triggers for asymptomatic intervention. Enthusiasm for early aortic valve replacement should be tempered by consideration of the competing risks of early valve intervention, but an increasing preponderance of evidence continues to suggest that earlier intervention in AS is warranted.

Catching a glimpse: Corona-life and its micro-politics in academia.

The spread of COVID-19 acutely challenges and affects not just economic markets, demographic statistics and healthcare systems, but indeed also the politics of organizing and becoming in a new everyday life of academia emerging in our homes. Through a collage of stories, snapshots, vignettes, photos and other reflections of everyday life, this collective contribution is catching a glimpse of corona-life and its micro-politics of multiple, often contradicting claims on practices as many of us live, work and care at home. It embodies concerns, dreams, anger, hope, numbness, passion and much more emerging amongst academics from across the world in response to the crisis. As such, this piece manifests a shared need to - together, apart - enact and explore constitutive relations of resistance, care and solidarity in these dis/organizing times of contested spaces, identities and agencies as we are living-working-caring at home during lockdowns.

Transcatheter Aortic Valve Implantation In Patients With a Large Aortic Annulus.

BACKGROUND: As the indications for transcatheter aortic valve implantation (TAVI) have expanded, so to have the demands on interventionists to allow as many patients to access this technology as possible. METHODS: We retrospectively reviewed our TAVI database for patients who had received a 29mm SAPIEN 3 valve despite having an annular area greater than the manufacturer-recommended upper limit of 683mm2, as determined by multi-detector computed tomography (MDCT). Procedural and inpatient outcome data were collected. RESULTS: The study population was 5 of 121 patients receiving a SAPIEN 3 valve since it became available in March 2015. Their annular area ranged from 691 to 800mm2. Valve deployment was successful in all patients. The deployment balloon volume was nominal, except for an additional 1ml in one patient. No patient had a new indication for permanent pacing, and no significant valvular or paravalvular regurgitation (PVR) was identified on post-procedure transthoracic echocardiography. All patients survived to hospital discharge. CONCLUSIONS: In this select group of patients we have demonstrated that it is safe and feasible to use the 29mm SAPIEN 3 in patients with annular dimensions greater than those recommended, with minimal balloon overfilling.

Early outcome of patients undergoing transcatheter aortic valve implantation (TAVI): The Auckland City Hospital experience 2011-2015.

AIMS: Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement (AVR) in high-risk patients. We report the initial TAVI experience at Auckland City Hospital. METHODS: The records of patients undergoing TAVI between 2011 and 2015 at Auckland City Hospital were reviewed. We report the procedural success and outcome, including major adverse events (death, stroke, myocardial infarction, bleeding, vascular complications and rehospitalisations), degree of aortic regurgitation and symptom status up to 1-year follow-up. RESULTS: Mean age was 80.7 years and mean Euroscore II and Society of Thoracic Surgeons' scores were 8.2% and 6.3% respectively; 50% had undergone previous cardiac surgery. Successful deployment of the valve was achieved in all patients. The cumulative mortality rates at 30 days, 6 months and 1 year were 2.4%, 6.1% and 12.2% and cumulative stroke rates 1.2%, 3% and 8.2% respectively. Severe aortic regurgitation occurred in 2.3% CONCLUSION: TAVI is available in the New Zealand public hospital system for patients who are high-risk candidates for AVR. Early results are excellent and indicate that the technology is being used appropriately, according to current access criteria. If the early cost effectiveness data are confirmed, the indications for TAVI may widen.

Recurrent Primary Cardiac Sarcoma Managed With Radical Cardiac Resection and Pneumonectomy.

Primary cardiac tumors are extremely rare. Although complete surgical resection of malignant primary cardiac tumors results in an improved survival compared with no intervention, the overall prognosis is generally poor, with treatable recurrent primary cardiac sarcomas being extremely rare. We report a patient with a recurrent primary cardiac sarcoma obstructing the left atrium managed with radical cardiac resection, including right pneumonectomy, with 21-month postprocedural survival.

Position statement for the operator and institutional requirements for a transcatheter aortic valve implantation (TAVI) program.

The Cardiac Society of Australia and New Zealand (CSANZ) and the Australia and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) have joined together to provide recommendations for institutions and individual operators to assess their ability to initiate and maintain a transcatheter valve program. Transcatheter aortic valve replacement has been developed as an alternative to traditional surgical replacement of the aortic valve in high risk patients, particularly the frail elderly. The position paper has endorsed the important role of a multi-disciplinary "Heart Team" in selecting patients for TAVI as fundamental to the establishment of a successful program. The paper outlines recommendations for the cardiologist to have a background in structural intervention and the surgeon to have experience in high-risk aortic valve replacement. It is further recommended that TAVI programs be established in high volume cardiac surgical centres where on site valve surgery is performed. The paper is intended to provide guidance to individual operators and prospective institutions considering the establishment of a successful TAVI program.

The right dorsal habenula limits attraction to an odor in zebrafish.

BACKGROUND: The habenula consists of an evolutionarily conserved set of nuclei that control neuromodulator release. In lower vertebrates, the dorsal habenula receives innervation from sensory regions, but the significance of this is unclear. Here, we address the role of the habenula in olfaction by imaging neural activity in larval zebrafish expressing GCaMP3 throughout the habenula and by carrying out behavioral assays. RESULTS: Activity in several hundred neurons throughout the habenula was recorded using wide-field fluorescence microscopy, fast focusing, and deconvolution. This enabled the creation of 4D maps of odor-evoked activity. Odors activated the habenula in two broad spatiotemporal patterns. Increasing concentrations of a putative social cue (a bile salt) evoked a corresponding increase in neuronal activity in the right dorsal habenula. In behavioral assays, fish were attracted to intermediate concentration of this cue but avoided higher concentration. Increasing cholinergic activity through nicotine exposure rendered the intermediate concentration aversive in a habenula-dependent manner. Pharmacologically blocking nicotinic receptors or lesioning the right dorsal habenula attenuated avoidance. CONCLUSIONS: These data provide physiological and functional evidence that the habenula functions as a higher center in zebrafish olfaction and suggest that activity in the right dorsal subdomain gates innate attraction to specific odors.

A randomised comparison of novolimus-eluting and zotarolimuselutingcoronary stents: 9-month follow-up results of the EXCELLA II study

Aims: Novolimus, a macrocyclic lactone with anti-proliferative properties, has asimilar efficacy to currently available agents; however it requires a lower dose,and less polymer, and is therefore conceivably safer.Methods and results: The EXCELLA II study was a prospective, multicentre,single-blind, non-inferiority clinical trial which randomised 210 patients with a maximum of two de novo coronary artery lesions in two different epicardialvessels in a ratio of 2:1 to treatment with either the Elixir DESyne NovolimusEluting Coronary Stent System (NES n=139, Elixir Medical, Sunnyvale, CA, USA)or the Endeavor zotarolimus eluting stent (ZES n=71, Medtronic, Santa Rosa, CA,USA). The primary endpoint was in-stent mean late lumen loss (LLL) at 9-monthsfollow-up. In-stent percent volume obstruction (%VO) was measured in asub-group of 65 patients having 9-month intravascular ultrasound (IVUS) follow-up.Clinical secondary endpoints included a device orientated composite of cardiacdeath, target vessel myocardial infarction (MI), and clinically indicated target lesionrevascularisation (CI-TLR) assessed at 9-months follow-up. At 9-months, thein-stent LLL was 0.11±0.32 mm in the NES arm, as compared to 0.63±0.42 mm inthe ZES (p<0.0001 non-inferiority, p<0.0001 superiority). In-stent%VO was4.5±5.1% and 20.9±11.3% for NES and ZES, respectively (p<0.001). There wasno significant difference between stent groups in the device orientated compositeendpoint (NES 2.9% vs. ZES 5.6%, –2.8% [-8.8%, 3.3%], p=0.45) or its individualcomponents of cardiac death, target vessel MI and CI-TLR.Conclusions: This non-inferiority randomised study not only met its primaryendpoint, but also demonstrated superiority of NES compared to the ZES in terms of in-stent LLL.

The Green Lane and Auckland City Hospital cardiac resynchronisation therapy experience.

AIM: To evaluate the outcome of cardiac resynchronisation therapy (CRT) in Auckland since its inception in 2000. Outcome measures were periprocedural events including procedure duration, fluoroscopic time, procedure success, complications, and echocardiographic markers of response. METHODS: Retrospective review of those undergoing CRT implantation at Green Lane and Auckland City Hospitals. RESULTS: 159 CRT procedures were performed on 139 patients between 2000 and April 2011. Of all procedures: 63% had new device implants, and 23% were upgraded from a pacemaker or defibrillator to CRT. Mean age 62 years, 77% male, mean left ventricular ejection fraction (LVEF) 25%, mean QRS duration 175 ms, 91% LBBB, 36% ischaemic cardiomyopathy. Mean procedure time 147 min and fluoroscopy time 30 min. Eight patients had significant periprocedural complications (6%), 17 experienced lead displacement (12%), and 15 (11%) had unsuccessful procedures. 46% of patients had complete echocardiographic data, of these LVEF improved by >5% in 52%, and decreased by >5% in 6% over a 16-month follow-up. CONCLUSIONS: Our service performs well with respect to complication rate, though less well when failure of implantation and lead dislodgement are considered. Where complete echocardiographic data was present 52% of our patients derived significant improvement in LVEF.

Safety and feasibility of patient transfer by helicopter for primary percutaneous coronary intervention.

AIM: Delayed treatment of patients undergoing transfer for primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) may reduce treatment benefits compared with fibrinolysis at the referring institution. We evaluated the feasibility of helicopter transfer of Whangarei patients to Auckland City Hospital for PPCI. METHOD: Clinical records of patients transferred from Whangarei to Auckland City Hospital by helicopter for PPCI were reviewed and clinical data reported. RESULTS: Between May 2010 and August 2011, 24 patients (19 male, median age 63 years, range 41-79 years) underwent helicopter transfer PPCI from Whangarei. Overall, median time to reperfusion was 125 minutes (IQR 117-147 minutes). For the 9 patients presenting within working hours (weekdays 8am-5pm), the median reperfusion time was 122 minutes (IQR 105-136 minutes), compared with 134 minutes (IQR 117-159 minutes) in the 15 patients presenting outside working hours. One patient achieved reperfusion within 90 minutes from presentation while 8/24 achieved reperfusion within 120 minutes. All patients survived to hospital discharge, as did 23/24 at 30 day follow-up. CONCLUSION: Helicopter transfer for PPCI from Whangarei to Auckland City Hospital is a feasible treatment strategy for patients presenting with STEMI. Improvements in treatment times are required if the full benefits of this strategy are to be realised.

Aortic stenosis: a contemporary review.

Aortic stenosis (AS) is the most common valvular disease in the western world affecting mainly individuals older than 60 years. It is recognized as an indolent disease characterized by years to decades of slow progression followed by rapid clinical deterioration and high mortality once symptoms develop. Medical therapies for AS remain ineffective with surgical aortic valve replacement (AVR) remaining the only proven effective long-term treatment. The advancement in transcatheter AVR has revolutionized the treatment of inoperable severe AS and holds promise for future widespread use as more long-term experience is established. The authors review the natural history of AS presentation with a special emphasis on management of severe AS and advancement in transcatheter AVR.

Cardiac sarcoid: a clinician's review on how to approach the patient with cardiac sarcoid.

Cardiac sarcoid is an infiltrative, granulomatous disease of the myocardium. It is more prevalent entity than once believed, especially subclinical disease. It affects heart mechanics causing ventricular failure, and disrupts the cardiac electrical system leading to third degree heart block, malignant ventricular arrhythmias, and sudden cardiac death. This makes early diagnosis and treatment of this devastating disease essential. Based on reviewed literature this paper proposes step-wise diagnostic and therapeutic algorithms for patients with suspected cardiac sarcoidoisis who do or do not have prior history of systemic sarcoidosis.

Transcatheter aortic valve implantation in end-stage renal disease.

Valvular heart disease is common in patients with end-stage renal disease and, if symptomatic, may lead to valve replacement surgery. However, some patients with renal failure are deemed unsuitable for cardiac surgery, and in those patients who do undergo surgery, there is a significantly greater morbidity and mortality. Transcatheter aortic valve implantation (TAVI) is recognized as an option for high-risk patients with symptomatic aortic stenosis (AS). Here we describe two patients on haemodialysis who underwent TAVI with satisfactory outcomes. The role of TAVI is evolving and has the potential to play an important role for dialysis patients with AS.

Patients assessing students' assignments; making the patient experience real.

The care of patients with inflammatory bowel disease (IBD) frequently falls short of the highest standards. This is noted in several publications, including national standards, despite nursing students being taught the importance of listening to and understanding patients. Teaching staff at the University of Glasgow primarily responsible for teaching third year undergraduate nursing students undertook a radical rethink of the planning, delivery and assessment of lectures on IBD. The subject had previously been delivered in a modified lecture format. Although the topic could be included in the end-of-year exams, there was little evidence to show whether this traditional teaching method had any effect on students' clinical practice. In a novel approach to learning and assessment, students were invited to research and produce an information leaflet for newly diagnosed patients with IBD. The leaflets were then assessed and grades awarded by an expert panel of patients and carers. Such enquiry based learning (EBL) intended to demonstrate in practice, the key role patients can play in both undergraduate nurse education and in service planning and delivery in the National Health Service (NHS). The panel found the exercise both interesting and insightful, while the students reported being invigorated and felt the expert assessment meant they were forced to achieve a higher level of work.

A randomised comparison of novolimus-eluting and zotarolimus-eluting coronary stents: 9-month follow-up results of the EXCELLA II study.

AIMS: Novolimus, a macrocyclic lactone with anti-proliferative properties, has a similar efficacy to currently available agents; however it requires a lower dose, and less polymer, and is therefore conceivably safer. METHODS AND RESULTS: The EXCELLA II study was a prospective, multicentre, single-blind, non-inferiority clinical trial which randomised 210 patients with a maximum of two de novo coronary artery lesions in two different epicardial vessels in a ratio of 2:1 to treatment with either the Elixir DESyne Novolimus Eluting Coronary Stent System (NES n=139, Elixir Medical, Sunnyvale, CA, USA) or the Endeavor zotarolimus eluting stent (ZES n=71, Medtronic, Santa Rosa, CA, USA). The primary endpoint was in-stent mean late lumen loss (LLL) at 9-months follow-up. In-stent percent volume obstruction (%VO) was measured in a?sub-group of 65 patients having 9-month intravascular ultrasound (IVUS) follow-up. Clinical secondary endpoints included a device orientated composite of cardiac death, target vessel myocardial infarction (MI), and clinically indicated target lesion revascularisation (CI-TLR) assessed at 9-months follow-up. At 9-months, the in-stent LLL was 0.11+/-0.32 mm in the NES arm, as compared to 0.63+/-0.42 mm in the ZES (p<0.0001 non-inferiority, p<0.0001 superiority). In-stent%VO was 4.5+/-5.1% and 20.9+/-11.3% for NES and ZES, respectively (p<0.001). There was no significant difference between stent groups in the device orientated composite endpoint (NES 2.9% vs. ZES 5.6%, -2.8% [-8.8%, 3.3%], p=0.45) or its individual components of cardiac death, target vessel MI and CI-TLR. CONCLUSIONS: This non-inferiority randomised study not only met its primary endpoint, but also demonstrated superiority of NES compared to the ZES in terms of in-stent LLL.

Pharmacogenetic testing for clopidogrel using the rapid INFINITI analyzer: a dose-escalation study.

OBJECTIVES: Our aim was to assess whether a higher clopidogrel maintenance dose has a greater antiplatelet effect in CYP2C19*2 allele carriers compared with noncarriers. BACKGROUND: Clopidogrel is a prodrug that is biotransformed by the cytochrome P450 enzymes CYP2C19, 2C9, and 3A4, 2B6, 1A2. The CYPC219*2 loss of function variant has been associated with a reduced antiplatelet response to clopidogrel and a 3-fold risk of stent thrombosis. METHODS: Forty patients on standard maintenance dosage clopidogrel (75 mg), for 9.4 +/- 9.2 weeks, were enrolled into a dose escalation study. Platelet function was assessed at baseline and after 1 week of 150 mg once daily using the VerifyNow platelet function analyzer (Accumetrics Ltd., San Diego, California). Genomic DNA was hybridized to a BioFilmChip microarray on the INFINITI analyzer (AutoGenomics Inc., Carlsbad, California) and analyzed for the CYP19*2, *4, *17, and CYP2C9*2, *3 polymorphisms. RESULTS: Platelet inhibition increased over 1 week, mean +8.6 +/- 13.5% (p = 0.0003). Carriers of the CYP2C19*2 allele had significantly reduced platelet inhibition at baseline (median 18%, range 0% to 72%) compared with wildtype (wt) (median 59%, range 11% to 95%, p = 0.01) and at 1 week (p = 0.03). CYP2C19*2 allele carriers had an increase in platelet inhibition of (mean +9 +/- 11%, p = 0.03) and reduction in platelet reactivity (mean -26 +/- 38 platelet response unit, p = 0.04) with a higher dose. Together CYP2C19*2 and CYP2C9*3 loss of function carriers had a greater change in platelet inhibition with 150 mg daily than wt/wt (+10.9% vs. +0.7%, p = 0.04). CONCLUSIONS: Increasing the dose of clopidogrel in patients with nonresponder polymorphisms can increase antiplatelet response. Personalizing clopidogrel dosing using pharmacogenomics may be an effective method of optimizing treatment.

Pain relief for the removal of femoral sheath in interventional cardiology adult patients.

BACKGROUND: There is considerable variation in use of pain relief for managing pain or discomfort of femoral sheath removal. Efficacy of pain relief to promote comfort during this procedure or to reduce the incidence of vascular and procedural complications has not been established. OBJECTIVES: Assess efficacy of pain relief used to manage pain of femoral sheath removal in adults after interventional cardiology.Determine if pain relief influences rate of complications associated with this procedure. SEARCH STRATEGY: Databases searched in August 2007: Cochrane Pain, Palliative and Supportive Care Group Trials Register, Cochrane Heart Group Trials Register, Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL, PubMed, Australia's Australasian Medical Index, National Research Centre, Web of Knowledge and Digital Dissertations. SELECTION CRITERIA: Randomised studies comparing opioid, local anaesthetic, anxiolytic, no treatment or placebo administered for alleviation of pain or discomfort of the femoral sheath removal procedure, were sought. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial quality and extracted data. Weighted mean differences (WMD) were calculated where meta-analysis of pain score data was feasible. Adverse effects information was collected. MAIN RESULTS: Four trials involving 971 participants were included. All results were reported using a zero to ten pain scale. Three trials (four treatment arms) involving 498 participants compared subcutaneous lignocaine with control; with no significant difference between pain scores; WMD 0.12 (95% CI -0.46 to 0.69). Two trials (three treatment arms) involving 399 participants compared intravenous pain regimens with control. A significant reduction in pain score with an intravenous pain regimen (opioid and anxiolytic) was observed when compared with placebo; WMD -0.90 (95% CI -1.54 to -0.27). One study involving 60 participants compared levobupivacaine with placebo. Longer-acting local anaesthetic significantly lowered pain score by -1.10 (95% CI -1.26 to -0.94). Data is insufficient to identify any influence of pain regimens on incidence of vascular and procedural complications. No trials reported appropriate blinding for treatment arms. The largest trial, comprising 661 participants was unblinded with a quality score of two out of five. AUTHORS' CONCLUSIONS: Intravenous pain regimens and levobupivacaine may have greater efficacy when compared to control for the management of pain related to femoral sheath removal. However, a definitive study is still required because the clinical difference is small. There is no evidence to support the use of subcutaneous lignocaine for the relief of femoral sheath removal related pain. There is insufficient evidence to determine if pain relief influences the rate of complications.

The antiplatelet effect of higher loading and maintenance dose regimens of clopidogrel: the PRINC (Plavix Response in Coronary Intervention) trial.

OBJECTIVES: This study evaluated the antiplatelet effect of a higher loading and maintenance dose regimen of clopidogrel and a possible drug interaction with verapamil. BACKGROUND: Clopidogrel loading doses above 600 mg have not resulted in more rapid or complete platelet inhibition. Higher maintenance dosages may be more effective than 75 mg/day. METHODS: A double-blind, randomized, placebo-controlled trial was undertaken in 60 patients undergoing percutaneous coronary intervention. All patients received clopidogrel 600 mg at the start of the procedure. Using a 2 x 2 design, patients were allocated to clopidogrel 600 mg given 2 h later or matching placebo, and to verapamil 5 mg intra-arterial or placebo. Platelet function was measured using the VerifyNow P2Y12 analyzer (Accumetrics Ltd., San Diego, California) at 2, 4, and 7 h. Patients were further randomized to receive a clopidogrel 75 or 150 mg once daily, with platelet function assessed after 1 week. RESULTS: Two hours after the second dose of clopidogrel or placebo, platelet inhibition was 42 +/- 27% with clopidogrel, compared with 24 +/- 22% with placebo (p = 0.0006). By 5 h after the second dose, platelet inhibition was 49 +/- 30% with clopidogrel, compared with 29 +/- 22% with placebo (p = 0.01). No drug interaction was seen with verapamil. A clopidogrel maintenance dosage of 150 mg daily for 1 week resulted in greater platelet inhibition than 75 mg daily (50 +/- 28% vs. 29 +/- 19%, p = 0.01). CONCLUSIONS: In an unselected population undergoing percutaneous coronary intervention a clopidogrel 1,200-mg loading dose, given as two 600-mg doses 2 h apart, results in more rapid and complete platelet inhibition than a single 600-mg dose. A maintenance dosage of 150 mg daily produces greater platelet inhibition than 75 mg daily. (The PRINC trial; ACTRN12606000129583).