The Role of Comorbidities in Predicting Functional Improvement After Transcatheter Aortic Valve Implantation.

BACKGROUND: Patients undergoing transcatheter aortic valve implantation (TAVI) have a high comorbidity burden. We sought to stratify patients into functional outcomes using the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), a patient-reported outcome with benefits over both the New York Heart Association (NYHA) classification and the original 23-item KCCQ, and to evaluate the importance of comorbidities in predicting failure of functional improvement post-TAVI in a contemporary cohort. METHODS: In total, 366 patients with severe aortic stenosis undergoing TAVI with baseline KCCQ-12 were retrospectively analysed and divided into two groups. Failure to improve was defined as a score <60 and a change in score <10 at 1 year in either overall score (KCCQ-OS) or clinical summary score (KCCQ-CSS). RESULTS: Failure to improve was noted in 13% of patients, who were more likely to have lower KCCQ-OS at baseline (47 [35-59] vs 56 [42-74]), chronic obstructive pulmonary disease (COPD) (19% vs 8%), severe chronic kidney disease (CKD) (13% vs 2%), a clinical frailty score (CFS) ≥5 (41% vs 14%), and lower serum albumin (36 g/L [34-38] vs 38 g/L [35-40]). On multivariate analysis, with an area under the curve of 0.71 (0.63-0.78), baseline KCCQ-OS (adjusted odds ratio [aOR] 0.3 [0.1-0.6], p=0.04), COPD (aOR 2.8 [1.2-6.5], p=0.02), and severe CKD (aOR 5.7 [1.7-18.5], p=0.004) remained independent predictors. CFS alone had a similar predictive value as the multivariable model (OR 2.0 [1.3-3.4], area under the curve 0.69 [0.59-0.80], p<0.001). CONCLUSIONS: KCCQ scores were effective in delineating functional outcomes, with most patients in our relatively lower surgical risk cohort showing significant functional improvements post-TAVI. Low baseline KCCQ, moderate or worse COPD, and severe CKD were associated with failure of improvement post-TAVI. Baseline CFS appears to be a good screening tool to predict poor improvement. These factors should be evaluated and weighted accordingly in pre-TAVI assessments and decision-making.

Post-Procedure Monocyte Count Levels Predict Major Adverse Cardiovascular Events (MACE) Following Transcatheter Aortic Valve Implantation (TAVI) for Aortic Stenosis.

BACKGROUND: Aortic stenosis has recently been characterised as having an inflammatory aetiology, beyond the traditional degenerative model. Recruitment of monocytes has been associated with inflammation contributing to progression of calcific aortic-valve disease. Prior research has demonstrated that pre-procedure inflammatory biomarkers do not consistently discriminate poorer outcomes in those with aortic stenosis. It remains, however, unclear if postprocedure inflammatory biomarkers, which are influenced by intraprocedural pro-inflammatory insults, can predict major adverse cardiovascular events (MACE) post transcatheter aortic valve implantation (TAVI). METHOD: All patients with postprocedure monocyte levels undergoing transcatheter aortic valve implantation at The Alfred Hospital, Melbourne, Australia (2008-2019) were included. The highest monocyte count from postprocedure days 1 to 3 was used. Patients were divided into "high" or "low" postprocedure monocyte count groups using the Youden Index. The incidence of 30-day MACE a composite of stroke, acute myocardial infarction, and death) was then compared. RESULTS: In total, 472 patients were included (54% men, median age 84 years). Fourteen (14) patients (3%) suffered a 30-day MACE. Those with high postprocedure monocyte count were more likely to: be hypertensive (p=0.049); have a higher Society of Thoracic Surgeons risk score (p=0.032); and, undergo non-transfemoral access (p=0.018). A high (≥0.975) postprocedure monocyte count was significantly associated with 30-day MACE (odds ratio [OR] 1.16 for each 0.1 increase in monocyte, p=0.025). This association remained present on multivariable analysis adjusted for age, sex, Society of Thoracic Surgeons risk score, and self-expanding valve prosthesis type (OR 1.17, p=0.028). CONCLUSIONS: The association between postprocedure monocytosis and 30-day MACE suggests that minimising peri-procedural inflammatory insults may improve outcomes. This inexpensive and readily available biomarker may also aid in tailored risk stratification for patients.

Acute Kidney Injury Following Transcatheter Aortic Valve Implantation-A Contemporary Perspective of Incidence, Predictors, and Outcomes.

BACKGROUND: Acute kidney injury (AKI) is a known complication following transcatheter aortic valve implantation (TAVI), associated with increased morbidity and mortality. Most of this data relates to higher-risk patients with early-generation TAVI valves. With TAVI now established as a safe and cost-effective procedure for low-risk patients, there is a distinct need for updated analysis. We aimed to assess the incidence, predictors, and outcomes of AKI in a contemporary cohort of TAVI patients, concurrently examining the role of temporal evolution on AKI. METHOD: A total of 2,564 patients undergoing TAVI from 2008-2023 included in the Alfred-Cabrini-Epworth (ACE) TAVI Registry were analysed. Patients were divided into AKI and no AKI groups. Outcomes were reported according to the Valve Academic Research Consortium-3 (VARC-3) criteria. RESULTS: Of 2,564 patients, median age 83 (78-87) years, 57.4% men and a median Society of Thoracic Surgeons score of 3.6 (2.4-5.5), 163 (6.4%) patients developed AKI with incidence falling from 9.7% between 2008-2014 to 6% between 2015-2023 (p=0.022). On multivariable analysis, independent predictors of AKI were male sex (adjusted odds ratio [aOR] 1.89, p=0.005), congestive cardiac failure (aOR 1.52, p=0.048), estimated glomerular filtration rate 30-59 (aOR: 2.79, p<0.001), estimated glomerular filtration rate <30 (aOR 8.65, p<0.001), non-femoral access (aOR 5.35, p<0.001), contrast volume (aOR 1.01, p<0.001), self-expanding valve (aOR 1.60, p=0.045), and bleeding (aOR 2.88, p=0.005). Acute kidney injury was an independent predictor of 30-day (aOR: 6.07, p<0.001) and 12-month (aOR: 3.01, p=0.002) mortality, an association that remained consistent when excluding TAVIs performed prior to 2015. CONCLUSIONS: Acute kidney injury remains a relatively common complication of TAVI, associated with significant morbidity and mortality even in less comorbid, contemporary practice patients.

Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial.

BACKGROUND: Renal denervation has been shown to lower blood pressure in the presence of antihypertensive medications; however, long-term safety and efficacy data from randomised trials of renal denervation are lacking. In this pre-specified analysis of the SPYRAL HTN-ON MED study, we compared changes in blood pressure, antihypertensive drug use, and safety up to 36 months in renal denervation versus a sham control group. METHODS: This randomised, single-blind, sham-controlled trial enrolled patients from 25 clinical centres in the USA, Germany, Japan, the UK, Australia, Austria, and Greece, with uncontrolled hypertension and office systolic blood pressure between 150 mm Hg and 180 mm Hg and diastolic blood pressure of 90 mm Hg or higher. Eligible patients had to have 24-h ambulatory systolic blood pressure between 140 mm Hg and less than 170 mm Hg, while taking one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned (1:1) to radiofrequency renal denervation or a sham control procedure. Patients and physicians were unmasked after 12-month follow-up and sham control patients could cross over after 12-month follow-up completion. The primary endpoint was the treatment difference in mean 24-h systolic blood pressure at 6 months between the renal denervation group and the sham control group. Statistical analyses were done on the intention-to-treat population. Long-term efficacy was assessed using ambulatory and office blood pressure measurements up to 36 months. Drug surveillance was used to assess medication use. Safety events were assessed up to 36 months. This trial is registered with ClinicalTrials.gov, NCT02439775; prospectively, an additional 260 patients are currently being randomly assigned as part of the SPYRAL HTN-ON MED Expansion trial. FINDINGS: Between July 22, 2015, and June 14, 2017, among 467 enrolled patients, 80 patients fulfilled the qualifying criteria and were randomly assigned to undergo renal denervation (n=38) or a sham control procedure (n=42). Mean ambulatory systolic and diastolic blood pressure were significantly reduced from baseline in the renal denervation group, and were significantly lower than the sham control group at 24 and 36 months, despite a similar treatment intensity of antihypertensive drugs. The medication burden at 36 months was 2·13 medications (SD 1·15) in the renal denervation group and 2·55 medications (2·19) in the sham control group (p=0·26). 24 (77%) of 31 patients in the renal denervation group and 25 (93%) of 27 patients in the sham control group adhered to medication at 36 months. At 36 months, the ambulatory systolic blood pressure reduction was -18·7 mm Hg (SD 12·4) for the renal denervation group (n=30) and -8·6 mm Hg (14·6) for the sham control group (n=32; adjusted treatment difference -10·0 mm Hg, 95% CI -16·6 to -3·3; p=0·0039). Treatment differences between the renal denervation group and sham control group at 36 months were -5·9 mm Hg (95% CI -10·1 to -1·8; p=0·0055) for mean ambulatory diastolic blood pressure, -11·0 mm Hg (-19·8 to -2·1; p=0·016) for morning systolic blood pressure, and -11·8 mm Hg (-19·0 to -4·7; p=0·0017) for night-time systolic blood pressure. There were no short-term or long-term safety issues associated with renal denervation. INTERPRETATION: Radiofrequency renal denervation compared with sham control produced a clinically meaningful and lasting blood pressure reduction up to 36 months of follow-up, independent of concomitant antihypertensive medications and without major safety events. Renal denervation could provide an adjunctive treatment modality in the management of patients with hypertension. FUNDING: Medtronic.

Avoiding the re-do sternotomy: treatment of an ascending aortic pseudoaneurysm using a percutaneous Amplatzer PFO closure device.

PURPOSE: Ascending aortic pseudoaneurysms are a common phenomenon requiring surgical intervention but can pose high surgical risks in medically complex patients. We report a novel approach to percutaneous closure of ascending aortic pseudoaneurysms using an Amplatzer PFO closure device. CASE REPORT: We present the case of a 65-year-old male with haemoptysis on a background of multiple cardiac surgeries and chronic kidney disease. Serial computerised tomography scans of the thoracic aorta demonstrated an enlarging ascending aortic pseudoaneurysm. Percutaneous closure was considered the safest treatment option. With angiography, the pseudoaneurysm was defined and a 25 mm Amplatzer PFO closure device was deployed. Repeat Computed Tomography aortography performed 43 days later confirmed stable device position and resolution of the pseudoaneurysm. The patient was clinically stable at this follow-up point. CONCLUSION: The off-label use of the Amplatzer PFO device may provide a viable alternative treatment for ascending aortic pseudoaneurysms in medically complex patients to reduce morbidity and mortality.

Long-Term Valve Durability in Patients Undergoing Transcatheter Aortic Valve Implantation.

AIMS: To evaluate the long-term incidence of structural valve deterioration (SVD) in patients who underwent transcatheter aortic valve implantation (TAVI). METHOD AND RESULTS: Between 2008 and 2018, 693 underwent TAVI at two centres. Four hundred and twenty-one (421) patients (mean age 83.6±6.0 yrs) survived for ≥2 years post TAVI and had at least two consecutive transthoracic echocardiographies (TTEs) with the latest TTE no less than 2 years after TAVI, and were therefore included in the analysis for SVD. Median follow-up was 4.7 (3.6-6.0) years and median echocardiography follow-up 3 (3.0-4.0) years. All-cause mortality was 30.9% (130) with a median time to death of 4.1 (3.0-5.6) years. The cumulative incidence of SVD increased from 1.7% (95% CI, 0.4-2.9) at 3 years to 3.5% (95% CI, 1.5-5.8) at 5 years and 4.7% (95% CI, 1.6-7.9) at 10 years. The overall median time to SVD was 3 (2-4) years. Twelve (12) patients demonstrated SVD stage 2, and 1 patient stage 3. No SVD required re-intervention. All other patients showed no significant changes in valve parameters over time. CONCLUSIONS: Structural valve deterioration is an uncommon event, occurring in 5% over a total follow-up of 10 years. Most patients show stable valve parameters. However, the analysis is limited by the loss of follow-up (owing to patient mortality), which renders extrapolation of the data to a younger patient population difficult.

Variability in Contemporary Heparin Prescription and Activated Clotting Time Monitoring During Percutaneous Coronary Intervention: Call for Up-To-Date Evidence-Based Guidelines.

BACKGROUND: Unfractionated heparin (UFH) is the preferred anticoagulant agent in percutaneous coronary intervention (PCI) procedures for minimising the risk of thrombotic complications. Because of the narrow therapeutic range of UFH, some society guidelines have advocated the use of the activated clotting time (ACT) test to monitor anticoagulation intensity during PCI to reduce thrombotic and bleeding complications. We aimed to assess the current practice of UFH prescription and its monitoring in Australia and New Zealand (ANZ). METHOD: We conducted an anonymous voluntary cross-sectional survey of interventional cardiologists (ICs) who were members of the Cardiac Society of Australia and New Zealand in 2022. The survey included 10 questions pertaining to the current practice of anticoagulation during PCI. RESULTS: Of 430 ICs surveyed, 148 responded (response rate, 34.4%). Most ICs (84.4%) prescribed 70-100 IU/kg of UFH for PCI. Over half of ICs (58.7%) routinely measured ACT during PCI, whereas only 22.2% routinely measured ACT after PCI to guide additional UFH prescription. Among ICs who prescribed additional UFH, approximately half (48%) aimed for ACT ≥250 seconds. Factors that influenced post-PCI UFH prescription included vascular access site and concomitant antiplatelet or anticoagulant therapy. CONCLUSIONS: The contemporary practice of UFH prescription during PCI and ACT monitoring in ANZ is variable and based on outdated evidence preceding current drug-eluting stents, antiplatelet therapies, and radial-first practice. Current society guideline recommendations lack clarity and agreement, reflecting the quality of the available evidence. Up-to-date clinical trials evaluating UFH prescription and ACT monitoring are needed to optimise clinical outcomes in contemporary PCI procedures.

Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis who are at increased risk for death from surgery; less is known about TAVR in low-risk patients. METHODS: We performed a randomized noninferiority trial in which TAVR with a self-expanding supraannular bioprosthesis was compared with surgical aortic-valve replacement in patients who had severe aortic stenosis and were at low surgical risk. When 850 patients had reached 12-month follow-up, we analyzed data regarding the primary end point, a composite of death or disabling stroke at 24 months, using Bayesian methods. RESULTS: Of the 1468 patients who underwent randomization, an attempted TAVR or surgical procedure was performed in 1403. The patients' mean age was 74 years. The 24-month estimated incidence of the primary end point was 5.3% in the TAVR group and 6.7% in the surgery group (difference, -1.4 percentage points; 95% Bayesian credible interval for difference, -4.9 to 2.1; posterior probability of noninferiority >0.999). At 30 days, patients who had undergone TAVR, as compared with surgery, had a lower incidence of disabling stroke (0.5% vs. 1.7%), bleeding complications (2.4% vs. 7.5%), acute kidney injury (0.9% vs. 2.8%), and atrial fibrillation (7.7% vs. 35.4%) and a higher incidence of moderate or severe aortic regurgitation (3.5% vs. 0.5%) and pacemaker implantation (17.4% vs. 6.1%). At 12 months, patients in the TAVR group had lower aortic-valve gradients than those in the surgery group (8.6 mm Hg vs. 11.2 mm Hg) and larger effective orifice areas (2.3 cm2 vs. 2.0 cm2). CONCLUSIONS: In patients with severe aortic stenosis who were at low surgical risk, TAVR with a self-expanding supraannular bioprosthesis was noninferior to surgery with respect to the composite end point of death or disabling stroke at 24 months. (Funded by Medtronic; ClinicalTrials.gov number, NCT02701283.).

Clinical outcomes according to lesion complexity in high bleeding risk patients treated with 1-month dual antiplatelet therapy following PCI: Analysis from the Onyx ONE clear study.

OBJECTIVES: To compare clinical outcomes in high bleeding risk (HBR) patients with and without complex percutaneous coronary intervention (PCI) treated with Resolute Onyx zotarolimus-eluting stents (ZES) after 1-month dual antiplatelet therapy (DAPT). BACKGROUND: PCI with 1-month DAPT has been demonstrated to be safe in HBR patients treated with Resolute Onyx ZES. Whether these outcomes are consistent in patients with complex lesions is uncertain. METHODS: Among HBR patients who were event-free 1 month after PCI with ZES and treated thereafter with single antiplatelet therapy (SAPT), the clinical outcomes between 1 month and 1 year were compared after complex PCI (3 vessels treated, ≥ 3 lesions treated, total stent length > 60 mm, bifurcation with ≥ 2 stents implanted, atherectomy, or left main, surgical bypass graft or chronic total occlusion PCI) versus noncomplex PCI. Propensity score adjustment was performed to adjust for baseline differences among complex and noncomplex patients. RESULTS: Complex patients (N = 401, 26.6% of total) had a higher prevalence of hyperlipidemia, diabetes mellitus and previous myocardial infarction (MI). Between 1 month and 1 year, rates of MI (7.1% vs. 4.0%, p = 0.02) and cardiac death/MI (9.3% vs. 6.1%, p = 0.04) were higher among complex versus noncomplex patients, although stent thrombosis rates were similar. After adjustment for baseline characteristics, differences in outcomes were no longer significant between groups. CONCLUSIONS: Higher rates of ischemic outcomes in complex PCI patients were largely explained by baseline clinical differences, rather than lesion complexity, among HBR patients treated with 1-month DAPT following PCI with Resolute Onyx ZES.

Sex-Specific Outcomes Following Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Left Main Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess whether outcomes following percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease differ between men and women. BACKGROUND: Current guidelines recommend either PCI or CABG for patients with unprotected LMCA disease and low-to-intermediate anatomical complexity. However, it is unclear whether these guidelines apply to women, who are underrepresented in clinical trials. METHODS: An electronic search was performed to identify studies reporting sex-specific outcomes after PCI versus CABG in patients with LMCA disease. Trial level hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled by random-effects modelling. RESULTS: Eight (8) studies met inclusion criteria, comprising 13,066 patients (24.3% women). In both sexes, there was no difference between PCI and CABG with respect to the primary composite endpoint of death, myocardial infarction or stroke (HR in women: 1.03, 95% CI 0.76-1.40; HR in men: 1.04, 95% CI 0.92-1.17). However, both sexes were more likely to require repeat revascularisation after PCI. There was no interaction between sex and treatment effect for the primary composite endpoint nor for the individual outcomes of death, stroke and repeat revascularisation. However, in women the risk of myocardial infarction was higher after PCI compared with CABG (HR 1.84, 95% CI 1.06-3.18), with a trend toward the opposite in men (HR 0.78, 95% CI 0.54-1.13; p-interaction=0.01). CONCLUSION: Percutaneous coronary intervention and CABG have a comparable risk of the composite outcome of death, stroke or myocardial infarction in patients undergoing revascularisation for LMCA disease, with no significant interaction between sex and treatment effect.

Adverse 30-Day Clinical Outcomes and Long-Term Mortality Among Patients With Preprocedural Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

OBJECTIVES: Approximately 5-10% of patients presenting for percutaneous coronary intervention (PCI) have concurrent atrial fibrillation (AF). To what extent AF portends adverse long-term outcomes in these patients remains to be defined. METHODS: We analysed data from the multicentre Melbourne Interventional Group Registry from 2014-2018. Patients were identified as being in AF or sinus rhythm (SR) at the commencement of PCI. The primary endpoint was long-term mortality, obtained via linkage with the National Death Index. RESULTS: 13,286 procedures were included, with 800 (6.0%) patients in AF and 12,486 (94.0%) in SR. Compared to SR, patients with AF were older (72.9±10.9 vs 64.1±12.0 p<0.001) and more likely to have comorbidities including diabetes mellitus (31.3% vs 25.0% p<0.001), hypertension (74.4% vs 65.1% p<0.001) and moderate to severe left ventricular systolic dysfunction (36.6% vs 19.5% p<0.001). Atrial fibrillation was associated with an increased risk of in-hospital mortality (11.0% vs 2.5% p<0.001) and MACE (composite of all-cause mortality, myocardial infarction, or target vessel revascularisation) (11.9% vs 4.2% p<0.001). In-hospital major bleeding was more common in the AF group (3.1% vs 1.0% p<0.001). On Cox proportional hazards modelling, AF was an independent predictor of long-term mortality (adjusted HR 1.38 95% CI 1.11-1.72 p<0.004) at a mean follow-up of 2.3±1.5 years. CONCLUSIONS: Preprocedural AF is common among patients presenting for PCI. Preprocedural AF is associated with high-rates of comorbid illnesses and portends higher risk of short- and long-term outcomes including mortality underscoring the need for careful evaluation of its risks prior to PCI.

Mitral Valve Regurgitation After Lung Transplantation: Aetiology, Management and Outcome.

BACKGROUND: Problematic mitral regurgitation (MR) may develop following lung transplantation (LTx). There is limited information on the management of MR in LTx patients, as such we sought to evaluate our centre's experience. METHODS: From 2000 to 2019, 1,054 patients underwent LTx at our centre (896 bilateral, 158 single). We identified patients in whom significant MR developed at any point post-LTx. The aetiology of MR, management and outcome were retrospectively analysed. RESULTS: Eight (8) patients developed severe MR post-LTx, six following bilateral LTx and two following single LTx. Lung transplantation indications included interstitial lung disease (n=5), chronic obstructive pulmonary disease (n=2) and pulmonary arterial hypertension (n=1). Severe MR occurred intraoperatively (n=1), postoperative day 1 (n=1) with the remaining six cases between 80 and 263 days post-LTx. The aetiology was noted to be due to severe left ventricular dysfunction following unmasking of a chronically pulmonary hypertension-related under-preloaded left ventricle in one case, and in the remaining seven patients causes included myxomatous degeneration, ischaemic MR, and functional MR due to annular dilatation. In the patient with intraoperative severe MR, the MR became mild with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and in the remaining seven patients a variety of procedures were used, including mitral valve repair, valve replacement and transcatheter edge-to-edge mitral valve repair. All patients survived the mitral procedure. Two (2) deaths occurred at 12.9 years (stroke) and 5 years (cancer) from mitral valve surgery. CONCLUSIONS: Development of significant mitral valve regurgitation is a rare but morbid complication after lung transplantation. This may represent the progressive natural history of pre-existing degenerative mitral valve disease and rarely, early after transplantation may be related to changes in ventricular geometry. Management of severe MR can follow the same management approach as in the non-transplant community, with the expectation of similarly good results.

Transcatheter Aortic Valve Implantation Represents an Anti-Inflammatory Therapy Via Reduction of Shear Stress-Induced, Piezo-1-Mediated Monocyte Activation.

BACKGROUND: Aortic valve stenosis is an increasingly prevalent degenerative and inflammatory disease. Transcatheter aortic valve implantation (TAVI) has revolutionized its treatment, thereby avoiding its life-threatening/disabling consequences. Whether aortic valve stenosis is accelerated by inflammation and whether it is itself a cause of inflammation are unclear. We hypothesized that the large shear forces exerted on circulating cells, particularly on the largest circulating cells, monocytes, while passing through stenotic aortic valves result in proinflammatory effects that are resolved with TAVI. METHODS: TAVI provides a unique opportunity to compare the activation status of monocytes under high shear stress (before TAVI) and under low shear stress (after TAVI). The activation status of monocytes was determined with a single-chain antibody, MAN-1, which is specific for the activated ß2-integrin Mac-1. Monocyte function was further characterized by the adhesion of myocytes to stimulated endothelial cells, phagocytic activity, uptake of oxidized low-density lipoprotein, and cytokine expression. In addition, we designed a microfluidic system to recapitulate the shear rate conditions before and after TAVI. We used this tool in combination with functional assays, Ca2+ imaging, siRNA gene silencing, and pharmacological agonists and antagonists to identify the key mechanoreceptor mediating the shear stress sensitivity of monocytes. Last, we stained for monocytes in explanted stenotic aortic human valves. RESULTS: The resolution of high shear stress through TAVI reduces Mac-1 activation, cellular adhesion, phagocytosis, oxidized low-density lipoprotein uptake, and expression of inflammatory markers in monocytes and plasma. Using microfluidics and pharmacological and genetic studies, we could recapitulate high shear stress effects on isolated human monocytes under highly controlled conditions, showing that shear stress-dependent calcium influx and monocyte adhesion are mediated by the mechanosensitive ion channel Piezo-1. We also demonstrate that the expression of this receptor is shear stress dependent and downregulated in patients receiving TAVI. Last, we show monocyte accumulation at the aortic side of leaflets of explanted aortic valves. CONCLUSIONS: We demonstrate that high shear stress, as present in patients with aortic valve stenosis, activates multiple monocyte functions, and we identify Piezo-1 as the mainly responsible mechanoreceptor, representing a potentially druggable target. We demonstrate an anti-inflammatory effect and therefore a novel therapeutic benefit of TAVI.

Cost-Effectiveness of Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients With Severe Aortic Stenosis.

BACKGROUND: Recent studies have shown that transcatheter aortic valve implantation (TAVI) is non-inferior to surgical aortic valve replacement (SAVR) for treatment of low-risk patients with severe aortic stenosis (AS). However, the cost-effectiveness of TAVI in this population is unknown. We sought to evaluate the cost-effectiveness of both balloon-expandable and self-expanding TAVI compared to SAVR in patients with severe AS at low operative risk. METHODS: We developed a Markov model comparing TAVI to SAVR over a lifetime horizon. Key data inputs were drawn from the Placement of AoRTic TraNscathetER Valve (PARTNER) 3 trial for balloon-expandable TAVI and the Evolut Low-Risk trial for self-expanding TAVI. Costs were obtained from Australian sources. The perspective was that of the Australian health care system. RESULTS: Although procedural costs were higher for TAVI compared to SAVR, these were offset by a shorter length of hospitalisation and lower acute complication costs in the TAVI group. Over a lifetime horizon, balloon-expandable TAVI was associated with increased costs of A$702 compared to SAVR, and increased quality-adjusted survival by 0.20 years, yielding an incremental cost-effectiveness ratio of A$3,521 per quality-adjusted life year (QALY) saved. Self-expanding TAVI was associated with lower lifetime costs compared to SAVR, and increased quality-adjusted survival by 0.08 years, and was therefore economically dominant. In probabilistic sensitivity analyses, balloon-expandable TAVI was cost-effective in 78% of iterations (at a cost-effectiveness threshold of A$50,000 per QALY gained) and self-expanding TAVI was cost-effective in 70% of iterations. CONCLUSIONS: Among low-risk AS patients, both balloon-expandable and self-expanding TAVI are likely to be cost-effective relative to SAVR.

Transcatheter Versus Surgical Aortic Valve Replacement: An Updated Systematic Review and Meta-Analysis With a Focus on Outcomes by Sex.

BACKGROUND AND AIMS: Women at increased surgical risk have been shown to have better outcomes with transcatheter aortic valve implantation (TAVI) as compared to surgical valve replacement (SAVR). With the scope of TAVI moving into low-surgical risk patients, we aimed to update the current literature to include the new low-risk randomised controlled trial (RCT) data in investigating outcomes by sex. METHODS: We systematically searched MEDLINE (Ovid), PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov and reference lists for relevant RCTs comparing TAVI to SAVR published prior to 4 May 2020. Data extraction was performed by two independent authors and included trial design details, baseline characteristics and outcome data stratified by sex. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool. Quantitative synthesis of pooled data was performed using Mantel-Haenszel fixed or random effects model. Q-statistic and the I2 test were used for assessment of heterogeneity. RESULTS: Our search yielded eight RCTs included in the final quantitative synthesis. The overall pooled cohort was 8,040, of whom 41.4% were female. Women had significantly lower rates of one-year all-cause mortality (12.2% vs 17.7%, pooled OR 0.59, 95% CI 0.40-0.86) and one-year composite endpoint (9.7% vs 12.4%, pooled OR 0.73, 95% CI 0.58-0.92) with TAVI as compared to SAVR. The selective mortality benefit with TAVI over SAVR in women did not persist to 5 years (pooled HR 1.01, 95% CI 0.87-1.17). At 30 days, women demonstrated lower rates of major bleeding and acute kidney injury following TAVI compared to SAVR. For men, these outcomes were similar regardless of type of intervention. Both sexes were at increased risk of major vascular complications with TAVI as compared to SAVR, however women demonstrated nearly double the odds of major vascular complication with TAVI compared to men. CONCLUSION: Our updated meta-analysis demonstrates that at one-year women undergoing TAVI have significantly lower mortality and better safety outcomes compared to those undergoing SAVR. These benefits are not seen in men. In the new low-risk era, these results are ever more important for guiding appropriate patient selection.

Operator and Institutional Requirements for Transcatheter Mitral Valve Therapies in Australia: a CSANZ and ANZSCTS Position Statement.

This expert Position Statement is a description of the requirements for Accreditation for transcatheter mitral valve therapy (TMVT) in Australia. The requirements include the need for a multidisciplinary Heart Team review of individual cases, mandatory reporting of outcome data to a national TMVT Registry, and accreditation of individuals and institutions by the Conjoint Accreditation Committee, the assigned accreditation authority.

Short- and Long-Term Outcomes After Transcatheter Aortic Valve Implantation in Public and Private Hospital Settings: A Propensity-Matched Analysis.

OBJECTIVES: To compare short- and long-term outcomes after transcatheter aortic valve implantation (TAVI) in the public and private hospital setting. DESIGN: Propensity-matched, retrospective analysis of a prospective registry. SETTING AND PARTICIPANTS: Patients with severe aortic stenosis who underwent TAVI at a tertiary public hospital (n=507) and an experienced private hospital (n=436). MAIN OUTCOME MEASURES: The primary endpoint was all-cause mortality. RESULTS: Patients that underwent TAVI in the public hospital were younger than patients in the private hospital (82±8 years vs 84±6 years, p<0.001), with lower estimated short-term mortality risk (Society of Thoracic Surgeons Predicted Risk of Mortality [STS-PROM] score >4.0%: 43% vs 56%, p<0.001). There was no difference between public and private hospitals in 30-day mortality (1.5% vs 1.2%, p=1.0), and the rate of complications was similar. Long-term survival was similar in propensity-matched public (n=344) and private (n=344) patient cohorts. The 1-year, 2-year, 5-year and 7-year survival rates were 95%, 90%, 67% and 47% in public patients, and 92%, 86%, 67% and 51% in private patients (p=0.94). In multivariable analysis, the hospital setting was not a predictor of mortality. CONCLUSION: Despite increased age and predicted mortality in private hospital patients, short- and long-term outcomes after TAVI were comparable between public and private hospital settings. This study demonstrates the feasibility of performing TAVI in a private hospital with a dedicated and experienced team and questions the current restricted access to TAVI in the private sector.

Effect of Age on Clinical Outcomes in Elderly Patients (>80 Years) Undergoing Percutaneous Coronary Intervention: Insights From a Multi-Centre Australian PCI Registry.

OBJECTIVES: To evaluate the effect of age in an all-comers population undergoing percutaneous coronary intervention (PCI). BACKGROUND: Age is an important consideration in determining appropriateness for invasive cardiac assessment and perceived clinical outcomes. METHODS: We analysed data from 29,012 consecutive patients undergoing PCI in the Melbourne Interventional Group (MIG) registry between 2005 and 2017. 25,730 patients <80 year old (78% male, mean age 62±10 years; non-elderly cohort) were compared to 3,282 patients ≥80 year old (61% male, mean age 84±3 years; elderly cohort). RESULTS: The elderly cohort had greater prevalence of hypertension, diabetes and previous myocardial infarction (all p<0.001). Elderly patients were more likely to present with acute coronary syndromes, left ventricular ejection fraction <45% and chronic kidney disease (p<0.0001). In-hospital, 30-day and long-term all-cause mortality (over a median of 3.6 and 5.1 years for elderly and non-elderly cohorts, respectively) were higher in the elderly cohort (5.2% vs. 1.9%; 6.4% vs. 2.2%; and 43% vs. 14% respectively, all p<0.0001). In multivariate Cox regression analysis, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (HR 3.8, 95% CI: 3.4-4.3), cardiogenic shock (HR 3.0, 95% CI: 2.6-3.4), ejection fraction <30% (HR 2.5, 95% CI: 2.1-2.9); and age ≥80 years (HR 2.8, 95% CI: 2.6-3.1) were independent predictors of long-term all-cause mortality (all p<0.0001). CONCLUSION: The elderly cohort is a high-risk group of patients with increasing age being associated with poorer long-term mortality. Age, thus, should be an important consideration when individualising treatment in elderly patients.

Cardiac Complications in Patients Hospitalised With COVID-19 in Australia.

OBJECTIVES: Describe the incidence of cardiac complications in patients admitted to hospital with COVID-19 in Australia. DESIGN: Observational cohort study. SETTING: Twenty-one (21) Australian hospitals. PARTICIPANTS: Consecutive patients aged ≥18 years admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MAIN OUTCOME MEASURES: Incidence of cardiac complications. RESULTS: Six-hundred-and-forty-four (644) hospitalised patients (62.5±20.1 yo, 51.1% male) with COVID-19 were enrolled in the study. Overall in-hospital mortality was 14.3%. Twenty (20) (3.6%) patients developed new atrial fibrillation or flutter during admission and 9 (1.6%) patients were diagnosed with new heart failure or cardiomyopathy. Three (3) (0.5%) patients developed high grade atrioventricular (AV) block. Two (2) (0.3%) patients were clinically diagnosed with pericarditis or myopericarditis. Among the 295 (45.8%) patients with at least one troponin measurement, 99 (33.6%) had a peak troponin above the upper limit of normal (ULN). In-hospital mortality was higher in patients with raised troponin (32.3% vs 6.1%, p<0.001). New onset atrial fibrillation or flutter (6.4% vs 1.0%, p=0.001) and troponin elevation above the ULN (50.3% vs 16.4%, p<0.001) were more common in patients 65 years and older. There was no significant difference in the rate of cardiac complications between males and females. CONCLUSIONS: Among patients with COVID-19 requiring hospitalisation in Australia, troponin elevation was common but clinical cardiac sequelae were uncommon. The incidence of atrial arrhythmias and troponin elevation was greatest in patients 65 years and older.

Outcomes of cardiogenic shock complicating acute coronary syndromes.

OBJECTIVES: We aimed to assess the outcomes of cardiogenic shock (CS) complicating acute coronary syndromes (ACS). BACKGROUND: CS remains the leading cause of mortality in patients presenting with ACS despite advances in care. METHODS: We studied 13,184 patients undergoing percutaneous coronary intervention (PCI) for all subtypes of ACS enrolled prospectively in a large multicentre Australian registry (Melbourne Interventional Group registry) from 2005 to 2013. All-cause mortality was obtained via linkage to the National Death Index. Patients were divided into those with and those without CS. RESULTS: Compared to the non-CS group (n = 12,548, 95.2%), the CS group (n = 636, 4.8%) had a higher proportion of out-of-hospital cardiac arrest (OHCA) (31.1 vs. 2.2%) and ST-elevation myocardial infarction (STEMI) presentation (89 vs. 34%), both p < .01. Patients in the CS group had higher rates of in-hospital (40.4 vs. 1.2%) and 30-day (41 vs. 1.7%) mortality compared to the non-CS group. Long-term mortality over a median follow-up of 4.2 years was higher in the CS group (50.6 vs. 13.8%), p < .001. Trends of in-hospital and 30-day mortality rates of CS complicating ACS were relatively stable from 2005 to 2013. Predictors of long-term NDI-linked mortality within the CS group include severe left ventricular systolic dysfunction (HR 3.0), glomerular filtration rate (GFR) <30 (HR 2.56), GFR 30-59 (HR 1.94), OHCA (HR 1.46), diabetes (HR 1.44), and age (HR 1.02), all p < .05. CONCLUSIONS: Rates of CS-related mortality complicating ACS have remained very high and steady over nearly a decade despite progress in STEMI systems of care, PCI techniques, and medical therapy.