Outcomes of thrombus aspiration during primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: Previous large multi-centre randomised controlled trials have not provided clear benefit with routine intracoronary thrombus aspiration (TA) as an adjunct to primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). AIM: To determine whether there is a difference in outcomes with the use of manual TA prior to PCI, compared with PCI alone in a cohort of patients with STEMI. METHODS: We analysed data from 6270 consecutive patients undergoing primary PCI for STEMI prospectively enrolled in the Melbourne Interventional Group registry between 2007 and 2018. Multivariable analysis was performed to determine predictors of 30-day major adverse cardiovascular and cerebrovascular events (MACCE) and long-term mortality. RESULTS: We compared 1621 (26%) patients undergoing primary PCI with TA to 4649 (74%) patients undergoing PCI alone. Male gender (81% vs 78%; P < 0.01), younger age (61 vs 63 years; P = 0.03), GP-IIb/IIIa use (76% vs 58%, P < 0.01), and current smoking (40% vs 36%; P < 0.01) were more common in the TA group. TA was more likely to be used in patients with complex lesions (83% vs 66%; P < 0.01) with TIMI 0 flow (77% vs 56%; P < 0.01). No significant difference in post-procedural TIMI flow, stroke, 30-day mortality, or long-term mortality were identified. Multivariable analysis demonstrated a reduction in 30-day MACCE (hazard ratio (HR) 0.75; confidence interval (CI) 0.63-0.89; P < 0.01) in the TA group, but was not associated with long-term mortality (HR 0.98; CI 0.85-1.1; P = 0.73). CONCLUSION: The use of TA in patients undergoing primary PCI for STEMI was not associated with improved short or long-term mortality when compared with PCI alone.

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.

Sex Differences in Pharmacotherapy and Long-Term Outcomes in Patients With Ischaemic Heart Disease and Comorbid Left Ventricular Dysfunction.

BACKGROUND: Left ventricular (LV) dysfunction and ischaemic heart disease (IHD) are common among women. However, women tend to present later and are less likely to receive guideline-directed medical therapy (GDMT) compared with men. METHODS: We analysed prospectively collected data (2005-2018) from a multicentre registry on GDMT 30 days after percutaneous coronary intervention in 13,015 patients with LV ejection fraction <50%. Guideline-directed medical therapy was defined as beta blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker±mineralocorticoid receptor antagonist. Long-term mortality was determined by linkage with the Australian National Death Index. RESULTS: Women represented 20% (2,634) of the total cohort. Mean age was 65±12 years. Women were on average >5 years, with higher body mass index and higher rates of hypertension, diabetes, renal dysfunction, prior stroke, and rheumatoid arthritis. Guideline-directed medical therapy was similar between sexes (73% vs 72%; p=0.58), although women were less likely to be on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (80% vs 82%; p=0.02). Women were less likely to be on statin therapy (p<0.001) or a second antiplatelet agent (p=0.007). Women had higher unadjusted long-term mortality (25% vs 19%; p<0.001); however, there were no differences in long-term mortality between sexes on adjusted analysis (hazard ratio 0.99; 95% confidence interval 0.87-1.14; p=0.94). CONCLUSIONS: Rates of GDMT for LV dysfunction were high and similar between sexes; however, women were less likely to be on appropriate IHD secondary prevention. The increased unadjusted long-term mortality in women was attenuated in adjusted analysis, which highlights the need for optimisation of baseline risk to improve long-term outcomes of women with IHD and comorbid LV dysfunction.

Harmonising Individual Patient Level Cardiac Registry Data Across the Asia Pacific Region-A Feasibility Study of In-Hospital Outcomes of STEMI Patients From the Asia Pacific Evaluation of Cardiovascular Therapies (ASPECT) Network.

OBJECTIVE: The Asia-Pacific Evaluation of Cardiovascular Therapies (ASPECT) collaboration was established to inform on percutaneous coronary intervention (PCI) in the Asia-Pacific Region. Our aims were to (i) determine the operational requirements to assemble an international individual patient dataset and validate the processes of governance, data quality and data security, and subsequently (ii) describe the characteristics and outcomes for ST-elevation myocardial infarction (STEMI) patients undergoing PCI in the ASPECT registry. METHODS: Seven (7) ASPECT members were approached to provide a harmonised anonymised dataset from their local registry. Patient characteristics were summarised and associations between the characteristics and in-hospital outcomes for STEMI patients were analysed. RESULTS: Six (6) participating sites (86%) provided governance approvals for the collation of individual anonymised patient data from 2015 to 2017. Five (5) sites (83%) provided >90% of agreed data elements and 68% of the collated elements had <10% missingness. From the registry (n=12,620), 84% were male. The mean age was 59.2±12.3 years. The Malaysian cohort had a high prevalence of previous myocardial infarction (34%), almost twice that of any other sites (p<0.001). Adverse in-hospital outcomes were the lowest in Hong Kong whilst in-hospital mortality varied from 2.7% in Vietnam to 7.9% in Singapore. CONCLUSIONS: Governance approvals for the collation of individual patient anonymised data was achieved with a high level of data alignment. Secure data transfer process and repository were established. Patient characteristics and presentation varied significantly across the Asia-Pacific region with this likely to be a major predictor of variations in the clinical outcomes observed across the region.

Long-term mortality in asymptomatic patients with stable ischemic heart disease undergoing percutaneous coronary intervention.

OBJECTIVES: Patients with stable ischemic heart disease (SIHD) may present with a variety of symptoms including typical angina, angina equivalents such as dyspnea or no symptoms. We sought to determine whether symptom status affects periprocedural safety and long-term mortality in patients undergoing PCI. METHODS: Prospectively enrolled consecutive patients undergoing PCI for SIHD at six hospitals in Australia between 2005 to 2018 as part of the Melbourne Interventional Group registry. Symptom status was recorded at the time of PCI and patients undergoing staged PCI were excluded. RESULTS: Overall, 11,730 patients with SIHD were followed up for a median period of 5 years (maximum 14.0 years, interquartile range 2.2-9.0 years) with 1,317 (11.2%) being asymptomatic. Asymptomatic patients were older, and more likely to be male, have triple-vessel disease, with multiple comorbidities including renal failure, diabetes and heart failure (all P < .01). These patients had significantly higher rates of periprocedural complications and major adverse cardiovascular events at 30-days. Long-term mortality was significantly higher in asymptomatic patients (27.2% vs 18.0%, P < .001). On cox regression for long-term mortality, after adjustment for more important clinical variables, asymptomatic status was an independent predictor (Hazard ratio (HR) 1.39 95% CI 1.16-1.66, P < .001). CONCLUSIONS: In a real-world cohort of patients undergoing revascularization for SIHD, absence of symptoms was associated with higher rates of periprocedural complications and, after adjustment for more important clinical variables, was an independent predictor of long-term mortality. As the primary goal of revascularization in SIHD remains angina relief, the appropriateness of PCI in the absence of symptoms warrants justification.

Characteristics and outcomes of unsuccessful percutaneous coronary intervention.

OBJECTIVES: To examine predictors and outcomes of unsuccessful percutaneous coronary intervention (PCI) cases in a contemporary Australian registry cohort. BACKGROUND: With improvements in techniques and pharmacotherapy in PCI, more complex lesions in older patients are now being attempted. In the context of PCI performance assessment, there are limited data regarding the characteristics and outcomes of unsuccessful PCI. METHOD: We prospectively collected data on patients undergoing single-lesion PCI between 2013 and 2017 who were enrolled in the multi-center Victorian Cardiac Outcomes Registry. Procedures were divided into two groups by whether or not PCI was deemed successful at the end of the procedure using a pre-specified definition. RESULTS: There were 34,383 single-lesion PCI performed, of which 18,644 (54.2%) were for acute coronary syndromes. Of the study cohort, 2080 patients (6.0%) had an unsuccessful PCI - these patients were older, more likely to have previous stroke, PCI, severe left ventricular dysfunction and chronic kidney disease (all p < 0.001). The procedure was also more likely to be performed for stable angina (p < 0.001). Chronic total occlusion PCI made up 31% of unsuccessful PCI cases. Unsuccessful PCI was itself associated with higher in-hospital and 30-day mortality and MACE (all p < 0.001). 4.9% of unsuccessful PCIs led to unplanned in-hospital bypass surgery (compared to 0.2% in successful PCIs, p < 0.001). CONCLUSION: Our study highlights that even in contemporary PCI practice, more than 1 in 20 PCI attempts are unsuccessful. Lack of procedural success has a strong influence on patient outcomes. Monitoring rates of unsuccessful cases is an important quality assurance tool.

Sex differences in prehospital analgesia in patients presenting with acute coronary syndromes and their association with clinical outcomes.

OBJECTIVES: This study examined if sex differences in prehospital pain scores, opioid administration, and clinical outcomes exist in acute coronary syndrome (ACS) patients. BACKGROUND: Sex differences persist in ACS presentation, management, and outcomes. The impact of sex differences on prehospital pain management of ACS with opioids is unknown. METHODS: Patients presenting with ACS via ambulance (2014-2018) that underwent percutaneous coronary intervention (PCI) were prospectively collected via the Victorian Cardiac Outcomes Registry and Melbourne Interventional Group, linked to the Ambulance Victoria database. The primary outcome was 30-day major adverse cardiac events (MACE). Secondary outcomes were descriptive analyses of prehospital pain score, intravenous morphine equivalent analgesic dosing, plus predictors of MACE and thrombolysis in myocardial infarction (TIMI) 0-1 flow pre-PCI. RESULTS: A total of 10,547 patients were included (female: 2775 [26%]). Opioids were administered to 1585 (57%) females, 5068 (65%) males (p < 0.001). Adjusted 30-day MACE was similar between opioid groups in both sexes (female: odds ratio [OR]: 1.21, confidence interval [CI] 0.82-1.79, p = 0.34; male: OR: 0.89, CI: 0.68-1.16, p = 0.40). Median pain score at presentation was 6 (interquartile range [IQR]: 4, 8) for both sexes. Median opioid dose was 2.5 mg (IQR: 0, 10) in females and 5 mg (IQR: 0, 10) in males (p < 0.001), with similar pain relief achieved. Adjusted rates of TIMI 0-1 pre-PCI were higher in patients administered opioids (female: OR 2.9, CI: 2.07-4.07, p < 0.001; male: OR: 2.67, CI: 2.19-3.25, p < 0.001). CONCLUSIONS: Female patients undergoing PCI received less opioid analgesia, but no sex differences in prehospital pain scores were seen. Opioid administration was associated with impaired antegrade flow in the culprit artery in both sexes, but not short-term MACE. Trials evaluating nonopioid analgesics in ACS are needed.

Health-related quality of life following percutaneous coronary intervention during the COVID-19 pandemic.

PURPOSE: During the COVID-19 pandemic, widespread public health measures were implemented to control community transmission. The association between these measures and health-related quality of life (HRQOL) among patients following percutaneous coronary intervention has not been studied. METHODS: We included consecutive patients undergoing percutaneous coronary intervention (PCI) in the state-wide Victorian Cardiac Outcomes Registry between 1/3/2020 and 30/9/2020 (COVID-19 period; n = 5024), with a historical control group from the identical period one year prior (control period; n = 5041). HRQOL assessment was performed via telephone follow-up 30 days following PCI using the 3-level EQ-5D questionnaire and Australian-specific index values. RESULTS: Baseline characteristics were similar between groups, but during the COVID-19 period indication for PCI was more common for acute coronary syndromes. No patients undergoing PCI were infected with COVID-19 at the time of their procedure. EQ-5D visual analogue score (VAS), index score, and individual components were higher at 30 days following PCI during the COVID-19 period (all P < 0.01). In multivariable analysis, the COVID-19 period was independently associated with higher VAS and index scores. No differences were observed between regions or stage of restrictions in categorical analysis. Similarly, in subgroup analysis, no significant interactions were observed. CONCLUSION: Measures of HRQOL following PCI were higher during the COVID-19 pandemic compared to the previous year. These data suggest that challenging community circumstances may not always be associated with poor patient quality of life.

Effects of lignocaine vs. opioids on antiplatelet activity of ticagrelor: the LOCAL trial.

AIMS: We assessed the impact of intravenous fentanyl and lignocaine on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with unstable angina and non-ST-elevation myocardial infarction and their procedural analgesic efficacy and safety. METHODS AND RESULTS: Seventy patients undergoing coronary angiography with ticagrelor loading were included in the pharmacokinetic and pharmacodynamic analyses of this randomized trial. Plasma ticagrelor levels 2 h post-loading dose were significantly lower in the fentanyl arm than in the lignocaine treatment arm (598 vs. 1008 ng/mL, P = 0.014). The area under the plasma-time curves for ticagrelor (1228 vs. 2753 ng h/mL, P < 0.001) and its active metabolite (201 vs. 447 ng h/mL, P = 0.001) were both significantly lower in the fentanyl arm. Expression of activated platelet glycoprotein IIb/IIIa receptor (2829 vs. 1426 mean fluorescence intensity, P = 0.006) and P-selectin (439 vs. 211 mean fluorescence intensity, P = 0.001) was significantly higher at 60 min in the fentanyl arm. A higher proportion of patients had high on-treatment platelet reactivity in the fentanyl arm at 60 min using the Multiplate Analyzer (41% vs. 9%, P = 0.002) and 120 min using the VerifyNow (30% vs. 3%, P = 0.003) and VASP (37% vs. 6%, P = 0.002) assays. Both drugs were well tolerated with a high level of patient satisfaction. CONCLUSIONS: Unlike fentanyl, lignocaine does not impair the bioavailability or delay the antiplatelet effect of ticagrelor. Both drugs were well tolerated and effective with a high level of patient satisfaction for procedural analgesia. Routine procedural analgesia during percutaneous coronary intervention should be reconsidered and if performed, lignocaine is a beneficial alternative to fentanyl.

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.

Trends and Real-World Safety of Patients Undergoing Percutaneous Coronary Intervention for Symptomatic Stable Ischaemic Heart Disease in Australia.

BACKGROUND: Percutaneous coronary intervention (PCI) in stable ischaemic heart disease (SIHD) has not been shown to improve prognosis but can alleviate symptoms and improve quality of life. Appropriately selected patients with symptoms refractory to medical therapy therefore stand to benefit, provided safety is proven. METHODS: Consecutive patients undergoing PCI for SIHD between 2005-2018 in a prospective registry were included. Yearly comparisons evaluated trends, and a sub-analysis was performed comparing proximal left anterior descending artery (prox-LAD) to other-than-proximal LAD (non-pLAD) PCI. Outcomes included peri-procedural characteristics, in-hospital and 30-day event rates including MACE, and 5-year National Death Index (NDI) linked mortality. RESULTS: There were 9,421 procedures included. Over time, patients were increasingly co-morbid and had higher rates of AHA/ACC class B2/C lesions, ostial stenoses, bifurcation lesions, and chronic total occlusions (all p-for-trend ≤0.001). Over 14 years, major bleeding reduced (1.05% in 2005/06 vs 0.29% in 2017/18, p-for-trend <0.001), while other in-hospital and 30-day event rates were stably low. There were only seven (0.07%) in hospital deaths and 5-year mortality was 10.3%. No differences were found in outcomes between patients who underwent prox-LAD compared to non-pLAD PCI. Major independent predictors of NDI linked all-cause mortality included an eGFR <30 mL/min/1.73 m2 (HR 4.06, 95% CI 3.26-5.06), chronic obstructive pulmonary disease (COPD) (HR 2.25, 95% CI 1.89-2.67) and LVEF <30% (HR 2.13, 95% CI 1.57-2.89). CONCLUSIONS: Although patient and procedural complexity increased over time, a high degree of procedural success and safety was maintained, including in those undergoing prox-LAD PCI. These real-world data can enhance shared decision making discussions regarding whether PCI should be pursued in patients with symptomatic SIHD refractory to medical therapy.

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.

Adverse impact of chronic kidney disease on clinical outcomes following percutaneous coronary intervention.

AIMS: We aimed to assess the impact of the severity of chronic kidney disease (CKD) with long-term clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). METHODS: We analyzed data on consecutive patients undergoing PCI enrolled in the Victorian Cardiac Outcomes Registry (VCOR) from January 2014 to December 2018. Patients were stratified into tertiles of renal function; estimated glomerular filtration (eGFR) ≥60, 30-59 and < 30 ml/min/1.73 m2 (including dialysis). The primary outcome was long-term all-cause mortality obtained from linkage with the Australian National Death Index (NDI). The secondary endpoint was a composite of 30 day major adverse cardiac and cerebrovascular events. RESULTS: We identified a total of 51,480 patients (eGFR ≥60, n = 40,534; eGFR 30-59, n = 9,521; eGFR <30, n = 1,425). Compared with patients whose eGFR was ≥60, those with eGFR 30-59 and eGFR<30 were on average older (77 and 78 vs. 63 years) and had a greater burden of cardiovascular risk factors. Worsening CKD severity was independently associated with greater adjusted risk of long-term NDI mortality: eGFR<30 hazard ratio 4.21 (CI 3.7-4.8) and eGFR 30-59; 1.8 (CI 1.7-2.0), when compared to eGFR ≥60, all p < .001. CONCLUSION: In this large, multicentre PCI registry, severity of CKD was associated with increased risk of all-cause mortality underscoring the high-risk nature of this patient cohort.

Prognostic significance of suboptimal secondary prevention pharmacotherapy after acute coronary syndromes.

BACKGROUND: Optimal secondary prevention pharmacotherapy is the cornerstone of post-acute coronary syndrome (ACS) management. The prognostic impact of not receiving five guideline-recommended therapies is poorly described. AIM: To ascertain the prognostic significance of suboptimal pharmacotherapy in ACS survivors. METHODS: Consecutive patients with ACS from the Melbourne Interventional Group registry who were alive at 30 days following their index percutaneous coronary intervention were included. Patients were divided into three categories based on the number of secondary prevention medications prescribed. The optimal medical therapy (OMT), near-optimal medical therapy (NMT), suboptimal medical therapy (SMT) groups were prescribed 5, 4 and ≤ 3 medications, respectively. Primary endpoint was long-term mortality. Cox-proportional hazard modelling was undertaken to assess independent predictors of survival. RESULTS: Of the 9375 patients included, 5678 (60.6%) received OMT, 2903 (31.0%) received NMT and 794 (8.5%) received SMT. Patients receiving SMT were older, more likely to be female and had higher burden of comorbidities (renal impairment, congestive heart failure, diabetes, peripheral vascular disease; P < 0.01 for all). SMT was associated with higher long-term mortality at 3.9 ± 2.2 years when compared to NMT and OMT (16.8% vs 10.5% vs 8.2%, P < 0.001). Compared to OMT, SMT was an independent predictor of long-term mortality (hazard ratio, HR 1.62, 95% confidence interval, CI 1.30-2.02, P < 0.01) while NMT was associated with a clinically significant 14% mortality hazard (HR 1.14, 95% CI 0.97-1.34, P = 0.11). CONCLUSIONS: There is a graded long-term hazard associated with not receiving OMT after an ACS. Improvements in secondary prevention pharmacotherapy models of care are warranted to further decrease the long-term mortality.

Applying a framework to assess the impact of cardiovascular outcomes improvement research.

BACKGROUND: Health and medical research funding agencies are increasingly interested in measuring the impact of funded research. We present a research impact case study for the first four years of an Australian National Health and Medical Research Council funded Centre of Research Excellence in Cardiovascular Outcomes Improvement (2016-2020). The primary aim of this paper was to explore the application of a research impact matrix to assess the impact of cardiovascular outcomes improvement research. METHODS: We applied a research impact matrix developed from a systematic review of existing methodological frameworks used to measure research impact. This impact matrix was used as a bespoke tool to identify and understand various research impacts over different time frames. Data sources included a review of existing internal documentation from the research centre and publicly available information sources, informal iterative discussions with 10 centre investigators, and confirmation of information from centre grant and scholarship recipients. RESULTS: By July 2019, the impact on the short-term research domain category included over 41 direct publications, which were cited over 87 times (median journal impact factor of 2.84). There were over 61 conference presentations, seven PhD candidacies, five new academic collaborations, and six new database linkages conducted. The impact on the mid-term research domain category involved contributions towards the development of a national cardiac registry, cardiovascular guidelines, application for a Medicare Benefits Schedule reimbursement item number, introduction of patient-reported outcome measures into several databases, and the establishment of nine new industry collaborations. Evidence of long-term impacts were described as the development and use of contemporary management for aortic stenosis, a cardiovascular risk prediction model and prevention targets in several data registries, and the establishment of cost-effectiveness for stenting compared to surgery. CONCLUSIONS: We considered the research impact matrix a feasible tool to identify evidence of academic and policy impact in the short- to midterm; however, we experienced challenges in capturing long-term impacts. Cost containment and broader economic impacts represented another difficult area of impact to measure.

Sex Disparities in Myocardial Infarction: Biology or Bias?

Women have generally worse outcomes after myocardial infarction (MI) compared to men. The reasons for these disparities are multifactorial. At the beginning is the notion-widespread in the community and health care providers-that women are at low risk for MI. This can impact on primary prevention of cardiovascular disease in women, with lower use of preventative therapies and lifestyle counselling. It can also lead to delays in presentation in the event of an acute MI, both at the patient and health care provider level. This is of particular concern in the case of ST elevation MI (STEMI), where "time is muscle". Even after first medical contact, women with acute MI experience delays to diagnosis with less timely reperfusion and percutaneous coronary intervention (PCI). Compared to men, women are less likely to undergo invasive diagnostic testing or PCI. After being diagnosed with a STEMI, women receive less guideline-directed medical therapy and potent antiplatelets than men. The consequences of these discrepancies are significant-with higher mortality, major cardiovascular events and bleeding after MI in women compared to men. We review the sex disparities in pathophysiology, risk factors, presentation, diagnosis, treatment, and outcomes for acute MI, to answer the question: are they due to biology or bias, or both?

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.

Sex Differences in Radial Access for Percutaneous Coronary Intervention in Acute Coronary Syndrome Are Independent of Body Size.

BACKGROUND: Radial access reduces bleeding and is associated with improved survival following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). We evaluated the association between sex, markers of body size and radial access, and its impact on bleeding and mortality following PCI for ACS. METHODS AND RESULTS: From 2013-2016, consecutive patients treated with PCI for ACS across 30 centres were prospectively entered into the Victorian Cardiac Outcomes Registry and followed for 30 days. Multivariate logistic regression was used to analyse predictors of the primary endpoint of PCI access site and secondary endpoints of major bleeding and mortality. A total of 16,330 ACS patients (40.9% ST elevation myocardial infarction [STEMI]) underwent PCI (23.5% female). Women were older with significantly lower weight and height compared to men. Women had lower radial access use (41.6% versus 51.0%, p<0.001), with higher 30-day major bleeding (2.4% versus 1.4%, p<0.001) and mortality (4.4% versus 3.4%, p<0.001) than men. Female sex independently predicted lower radial access use (OR 0.75, 95% CI 0.68-0.83, p<0.001) while body surface area, height and body mass index did not. Female sex was an independent predictor of higher 30-day major bleeding (OR 1.38, 95% CI 1.05-1.81, p=0.019) and mortality in STEMI patients (OR 1.31, 95% CI 1.01-1.70. p=0.039). Radial access was associated with lower major bleeding (OR 0.70, 95% CI 0.53-0.91, p=0.009) and mortality (OR 0.60, 95% CI 0.48-0.75, p<0.001). CONCLUSIONS: Radial access, despite being associated with lower bleeding and mortality, was used less frequently in women, independent of co-morbidities and objective markers of body size.