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.

Incidence and Predictors of Eosinophilic Myocardial Hypersensitivity in Patients Receiving Home Dobutamine.

ABSTRACT: We sought to examine incidence and predictors of eosinophilic myocardial hypersensitivity (EMH) in a cohort of patients in the home inotrope program of a quaternary cardiac transplant center. Patients on home inotropes with progression to heart transplantation or ventricular assist device (VAD) between January 2000 and May 2020 were included. EMH was diagnosed by the presence of an interstitial predominate eosinophilic infiltrate within the myocardium by experienced cardiac pathologists. From a cohort of 74 patients, 58% (43) were on dobutamine and 42% (31) were on milrinone. Dobutamine was associated with EMH incidence of 14% (6/43), with zero cases in the milrinone cohort. Mean age was 52 ± 12 years, 22% were female. More than half (62%) were nonischemic dilated cardiomyopathies, the remainder were ischemic cardiomyopathy. Dobutamine dose [250 (200-282) vs. 225 (200-291) µg/min] and duration of therapy [41 (23-79) vs. 53 (24-91) days] was similar between those with and without EMH. Median change in eosinophil count was 0.31 × 10 9 /L in the EMH group compared with only 0.03 × 10 9 /L in the non-EMH cohort, P = 0.02. Increase in peripheral eosinophil count of >0.20 × 10 9 /L demonstrated good discrimination between those with and without EMH, c-statistic 0.83 (95% CI 0.66-1.0). Heart failure hospitalization occurred in 83% of the EMH group versus 59% in the non-EMH group, P = 0.26. Requirement for VAD was significantly higher in the EMH group (83% vs. 41%, P = 0.05). In conclusion, EMH occurred in 14% of patients receiving home dobutamine. Rising eosinophil count should prompt physicians to consider EMH and switch to milrinone to avoid possible escalation to VAD.

Levosimendan and Continuous Outpatient Support With Inotropes in Patients With Advanced Heart Failure: A Single-Centre Descriptive Study.

ABSTRACT: To describe the use of levosimendan in a quaternary referral center with a dedicated heart failure service and compare its efficacy and safety to continuous outpatient support with inotropes (COSI) among patients with advanced heart failure (AHF) who require bridge-to-decision (BTD) or bridge-to-transplant (BTT) therapy. This study was a retrospective, single-center, descriptive study of patients with AHF who received either a single levosimendan infusion or COSI between 2018 and 2021. A total of 23 patients received a levosimendan infusion, and 14 were started on COSI. Three indications for levosimendan were identified: (1) to facilitate weaning of continuous inotropes, (2) to augment diuresis in cardiorenal syndrome, and (3) as first-line therapy for cardiogenic shock in selected patients. Eighty-three percent (19 of 23) of patients who received levosimendan survived to discharge, and there were few clinically significant adverse events. Overall survival at 12 months among patients who received levosimendan was 74%. No statistically significant difference in survival was observed at 12 months (P = 0.68) or beyond (P = 0.63) between patients who received levosimendan and were discharged with a plan for BTD or BTT and those who received COSI. Levosimendan is a safe and effective short-term therapy in AHF and offers comparable long-term survival to COSI in patients who require BTD or BTT therapy.

Temperature Management and Health-Related Quality of Life in Children 3 Years After Cardiac Arrest.

OBJECTIVES: Therapeutic hypothermia minimizes neuronal injury in animal models of hypoxic-ischemic encephalopathy with greater effect when used sooner after the insult. Clinical trials generally showed limited benefit but are difficult to perform in a timely manner. In this clinical study, we evaluated the association between the use of hypothermia (or not) and health-related quality of life among survivors of pediatric cardiac arrest as well as overall mortality. DESIGN: Single-center, retrospectively identified cohort with prospective assessment of health-related quality of life. SETTING: PICU of a pediatric hospital. PATIENTS: Children with either out-of-hospital or in-hospital cardiac arrest from January 2012 to December 2017. INTERVENTIONS: Patients were assigned into two groups: those who received therapeutic hypothermia at less than or equal to 35°C and those who did not receive therapeutic hypothermia but who had normothermia targeted (36-36.5°C). The primary outcome was health-related quality of life assessment and the secondary outcome was PICU mortality. MEASUREMENTS AND MAIN RESULTS: We studied 239 children, 112 (47%) in the therapeutic hypothermia group. The median (interquartile range) of lowest temperature reached in the 48 hours post cardiac arrest in the therapeutic hypothermia group was 33°C (32.6-33.6°C) compared with 35.4°C (34.7-36.2°C) in the no therapeutic hypothermia group (p < 0.001). At follow-up, 152 (64%) were alive and health-related quality of life assessments were completed in 128. Use of therapeutic hypothermia was associated with higher lactate and lower pH at baseline. After regression adjustment, therapeutic hypothermia (as opposed to no therapeutic hypothermia) was associated with higher physical (mean difference, 15.8; 95% CI, 3.5-27.9) and psychosocial scores (13.6 [5.8-21.5]). These observations remained even when patients with a temperature greater than 37.5°C were excluded. We failed to find an association between therapeutic hypothermia and lower mortality. CONCLUSIONS: Out-of-hospital or in-hospital cardiac arrest treated with therapeutic hypothermia was associated with higher health-related quality of life scores despite having association with higher lactate and lower pH after resuscitation. We failed to identify an association between use of therapeutic hypothermia and lower mortality.

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.

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.

Changing Risk of In-Hospital Cardiac Arrest in Children Following Cardiac Surgery in Victoria, Australia, 2007-2016.

BACKGROUND: Reported incidence of in hospital cardiac arrest (IHCA) after paediatric cardiac surgery varies between 3-4% in high income countries and this risk may have changed over time. We sought to examine this trend in detail. METHODS: A retrospective observational study of 3,781 children who underwent 4,938 cardiac surgeries between 1 January 2007 and 31 December 2016 in a tertiary children's hospital. IHCA was defined as cessation of cardiac mechanical activity requiring cardiac massage for ≥1minute. Surgical complexity was categorised using risk adjusted congenital heart surgery (RACHS-1) category. Poisson regression was used to analyse trends for every two-year period. RESULTS: There were a total of 211 (4.3%) IHCA events after surgery. These patients were younger, more likely to have had a premature birth, have a chromosomal or genetic syndrome association and have a high surgical complexity. Overall, there was a 52% reduction in IHCA rate over 10 years: reducing from 5.4 /100 surgeries in 2007-08 to 2.6/100 surgeries in 2015-16 (p-trend=<0.001). The reduction was mainly seen in low-to-moderate risk categories (RACHS-1 categories 1-4) and not in high risk categories (RACHS-1 category 5-6). Children in high risk categories were 13.6 times more likely to experience an IHCA (compared to low risk categories). Overall hospital mortality for children suffering IHCA decreased from 42.5/100 patients in 2007-08 to 11.1/100 patients in 2015-16 (p-trend=0.037). CONCLUSIONS: The IHCA rate following cardiac surgery has more than halved over the last decade; children who experience IHCA also have lower mortality than in previous years. High risk procedures still have a substantial rate of IHCA and efforts are needed to minimise the burden further in this population.

Factors That Prevent Progression to Transcatheter Aortic Valve Implantation (TAVI).

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is increasingly used for intermediate- and high-risk patients with severe symptomatic aortic stenosis (AS). However, safe undertaking of the procedure may be precluded by various anatomic factors. This study sought to identify prevalence of factors that prevent progression to TAVI. METHODS: TAVI candidates with severe AS undergoing workup coronary angiography and iliac vessel angiography (±cardiac-gated CT) were identified and factors precluding TAVI were reviewed retrospectively from a single-centre cardiac database over a 10-year period. RESULTS: 197 patients were included; mean age was 81.5±6.5years (±SD); 46.2% were male. 26.9% of TAVI candidates could not proceed to femoral access TAVI due to various factors including unsuitable peripheral vasculature (13.2%), untreated coronary artery disease (CAD) deemed high risk for TAVI (8.1%), unfavourable aortic characteristics (4.1%), and low-lying coronary ostia (1.5%). Factors associated with unsuitable femoral vasculature included female gender (p<0.01) and any CAD (p=0.03). Factors associated with the presence of unrevascularised CAD included male gender (p<0.01), estimated glomerular filtration rate (eGFR)<30mL/min/1.73m2 (p=0.02), history of CAD (p<0.01), while prior percutaneous coronary intervention (PCI) or bypass surgery were protective (both p<0.01). Rates of progression to TAVI have increased over the last 10 years (p<0.01) from 58.3% prior to 2012 to 83.7% in 2016 and 2017, while incidence of unsuitable peripheral vasculature preventing TAVI (p=0.01) and CAD deemed unsuitable for TAVI (p=0.04) have both decreased. CONCLUSIONS: Non-progression to TAVI among higher risk patients with severe AS has become less common over the last 10 years with improvements in operator experience, lower profile devices, and wider ranges of valve sizes.

Waiting times of women vs. men undergoing transcatheter aortic valve implantation.

AIMS: Increasing transcatheter aortic valve implantation (TAVI) rates have resulted in prolonged waiting times. These have been associated with heart failure hospitalizations (HFH) and mortality yet sex differences have not yet been reported. METHODS AND RESULTS: All patients who underwent TAVI for severe aortic stenosis at a tertiary referral hospital in Australia were prospectively included. Total waiting time was divided into 'work-up' waiting time (period from referral date until heart team approval) and, 'procedural' waiting time (period from heart team approval until procedure date). Patients were analysed according to sex. Cohorts were matched to correct for differences in baseline and procedural variables. The primary endpoints were waiting times. Secondary outcomes included a composite of 30-day mortality and HFH, quality of life, and mobility. A total of 407 patients (42% women) were included. After matching of the two cohorts (345 patients), women had significantly longer total waiting times than men: median 156 [interquartile range (IQR) 114-220] days in women vs. 147 [IQR 92-204] days in men (P = 0.037) including longer work-up (83 [IQR 50-128] vs. 71 [IQR 36-119], P = 0.15) and procedural waiting times (65 [IQR 44-100] vs. 58 [IQR 30-93], P = 0.042). Increasing waiting times were associated with higher 30-day mortality and HFH (P = 0.01 for work-up waiting time, P = 0.02 for procedural waiting time) and decreased 30-day mobility (P = 0.044 for procedural waiting time) in women, but not in men. CONCLUSION: TAVI waiting times are significantly longer in women compared to men and are associated with increased mortality and HFH and reduced mobility at 30-days.

Coronary Artery Disease Risk Prediction in Patients With Severe Aortic Stenosis: Development and Validation of the Aortic Stenosis-Coronary Artery Disease (AS-CAD) Score.

Patients at a low risk of coronary artery disease (CAD) could be triaged to noninvasive coronary computed tomography angiogram instead of invasive coronary angiography, reducing health care costs and patient morbidity. Therefore, we aimed to develop a CAD risk prediction score to identify those who underwent transcatheter aortic valve implantation (TAVI) at a low risk of CAD. We enrolled 1,782 patients who underwent TAVI and randomized the patients to the derivation or validation cohort 2:1. The aortic stenosis-CAD (AS-CAD) score was developed using logistic regression, followed by separation into low- (score 0 to 5), intermediate- (6 to 10), or high-risk (>11) categories. The AS-CAD was validated initially through the k-fold cross-validation, followed by a separately held validation cohort. The average age of the cohort was 82 ± 7 years, and 41% (730 of 1,782) were female; 35% (630) had CAD. The male sex, previous percutaneous coronary intervention, stroke, peripheral arterial disease, diabetes, smoking status, left ventricular ejection fraction <50%, and right ventricular systolic pressure >35 mm Hg were all associated with an increased risk of CAD and were included in the final AS-CAD model (all p <0.03). Within the validation cohort, the AS-CAD score stratified those into low, intermediate, and high risk of CAD (p <0.001). Discrimination was good within the internal validation cohort, with a c-statistic of 0.79 (95% confidence interval 0.74 to 0.84), with similar power obtained using k-fold cross-validation (c-statistic 0.74 [95% confidence interval 0.70 to 0.77]). In conclusion, The AS-CAD score robustly identified those at a low risk of CAD in patients with severe AS. The use of AS-CAD in practice could avoid potential complications of invasive coronary angiogram by triaging low-risk patients to noninvasive coronary assessment using existing computed tomography data.

Impact of Preprocedural Diastolic Blood Pressure on Outcomes in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Recent US guidelines recommend lower blood pressure (BP) targets in hypertension, but aggressive lowering of diastolic BP (DBP) can occur at the expense of myocardial perfusion, particularly in the presence of coronary artery disease. We sought to establish the long-term impact of low DBP on mortality among patients undergoing percutaneous coronary intervention with well-controlled systolic BP. METHODS: We analyzed data from 12 965 patients undergoing percutaneous coronary intervention between 2009 and 2018 from the Melbourne Interventional Group registry who had a preprocedural systolic BP of ≤140 mm Hg. Patients with ST-elevation myocardial infarction, cardiogenic shock, and out-of-hospital arrest were excluded. Patients were stratified into 5 groups according to preprocedural DBP: <50, 50 to 59, 60 to 69, 70 to 79, and ≥80 mm Hg. The primary outcome was long-term, all-cause mortality. Mortality data were derived from the Australian National Death Index. RESULTS: Patients with DBP<50 mm Hg were older with higher rates of diabetes, renal impairment, prior myocardial infarction, left ventricular dysfunction, peripheral and cerebrovascular disease (all P<0.001). Patients with DBP<50 mm Hg had higher 30-day (2.5% versus 0.7% for the other 4 quintiles; P<0.0001) and long-term mortality (median, 3.6 years; follow-up, 29% versus 11%; P<0.0001). Cox-regression analysis revealed that DBP<50 mm Hg was an independent predictor of long-term mortality (hazard ratio [HR], 1.55 [95% CI, 1.20-2.00]; P=0.001). CONCLUSIONS: In patients with well-controlled systolic BP undergoing percutaneous coronary intervention, low DBP (<50 mm Hg) is an independent predictor of long-term mortality.

Trends in Intra-Aortic Balloon Pump Use in Cardiogenic Shock After the SHOCK-II Trial.

Myocardial infarction complicated by cardiogenic shock (MI-CS) has a poor prognosis, even with early revascularization. Previously, intra-aortic balloon pump (IABP) use was thought to improve outcomes, but the IABP-SHOCK-II (Intra-aortic Balloon Pump in Cardiogenic Shock-II study) trial found no survival benefit. We aimed to determine the trends in IABP use in patients who underwent percutaneous intervention over time. Data were taken from patients in the Melbourne Interventional Group registry (2005 to 2018) with MI-CS who underwent percutaneous intervention. The primary outcome was the trend in IABP use over time. The secondary outcomes included 30-day mortality and major adverse cardiovascular and cerebrovascular events (MACCEs). Of the 1,110 patients with MI-CS, IABP was used in 478 patients (43%). IABP was used more in patients with left main/left anterior descending culprit lesions (62% vs 46%), lower ejection fraction (<35%; 18% vs 11%), and preprocedural inotrope use (81% vs 73%, all p <0.05). IABP use was associated with higher bleeding (18% vs 13%) and 30-day MACCE (58% vs 51%, both p <0.05). The rate of MI-CS per year increased over time; however, after 2012, there was a decrease in IABP use (p <0.001). IABP use was a predictor of 30-day MACCE (odds ratio 1.6, 95% confidence interval 1.18 to 2.29, p = 0.003). However, IABP was not associated with in-hospital, 30-day, or long-term mortality (45% vs 47%, p = 0.44; 46% vs 50%, p = 0.25; 60% vs 62%, p = 0.39). In conclusion, IABP was not associated with reduced short- or long-term mortality and was associated with increased short-term adverse events. IABP use is decreasing but is predominately used in sicker patients with greater myocardium at risk.

Differences in outcomes of patients with in-hospital versus out-of-hospital ST-elevation myocardial infarction: a registry analysis.

OBJECTIVES: Patients with ST-elevation myocardial infarction (STEMI) that occur while already in hospital ('in-hospital STEMI') face high mortality. However, data about this patient population are scarce. We sought to investigate differences in reperfusion and outcomes of in-hospital versus out-of-hospital STEMI. DESIGN, SETTING AND PARTICIPANTS: Consecutive patients with STEMI all treated with percutaneous coronary intervention (PCI) across 30 centres were prospectively recruited into the Victorian Cardiac Outcomes Registry (2013-2018). PRIMARY AND SECONDARY OUTCOMES: Patients with in-hospital STEMI were compared with patients with out-of-hospital STEMI with a primary endpoint of 30-day major adverse cardiovascular events (MACE). Secondary endpoints included ischaemic times, all-cause mortality and major bleeding. RESULTS: Of 7493 patients with PCI-treated STEMI, 494 (6.6%) occurred in-hospital. Patients with in-hospital STEMI were older (67.1 vs 62.4 years, p<0.001), more often women (32% vs 19.9%, p<0.001), with more comorbidities. Patients with in-hospital STEMI had higher 30-day MACE (20.4% vs 9.8%, p<0.001), mortality (12.1% vs 6.9%, p<0.001) and major bleeding (4.9% vs 2.3%, p<0.001), than patients with out-of-hospital STEMI. According to guideline criteria, patients with in-hospital STEMI achieved symptom-to-device times of ≤70 min and ≤90 min in 29% and 47%, respectively. Patients with out-of-hospital STEMI achieved door-to-device times of ≤90 min in 71%. Occurrence of STEMI while in hospital independently predicted higher MACE (adjusted OR 1.77, 95% CI 1.33 to 2.36, p<0.001) and 12-month mortality (adjusted OR 1.49, 95% CI 1.08 to 2.07, p<0.001). CONCLUSIONS: Patients with in-hospital STEMI experience delays to reperfusion with significantly higher MACE and mortality, compared with patients with out-of-hospital STEMI, after adjustment for confounders. Focused strategies are needed to improve recognition and outcomes in this high-risk and understudied population.

Periprocedural Myocardial Injury and Coronary Artery Disease in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND/PURPOSE: PPMI and CAD are common in patients undergoing TAVR. Despite several studies evaluating their interaction as well as the influence these factors play on outcomes, there remains no consensus. We sought to evaluate the impact of peri-procedural myocardial injury (PPMI) and incidental coronary artery disease (iCAD) on outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS/MATERIALS: We analyzed prospective data from 400 patients undergoing TAVI for severe aortic stenosis between 2008 and 2018 to determine rates of PPMI (troponin 15× the upper limit of normal) and iCAD (≥50% stenosis) and their impact on long-term mortality. RESULTS: Mean age was 83 ± 6 years; 45% were female. PPMI was observed in 65% (254/400). On multivariable logistic regression analysis, higher left ventricular ejection fraction (LVEF) (OR 1.04, 95%CI 1.01-1.06, p = 0.002), and first generation valves (OR 3.00, 95%CI 1.75-5.15, p < 0.001) were independently associated with PPMI, while oral anticoagulation was inversely associated (OR 0.48, 95%CI 0.28-0.82, p = 0.007). PPMI was not associated with 30-day, 1-year or long-term mortality. After excluding previous bypass grafting, iCAD was observed in 40% (129/324). In patients with iCAD, PCI was associated with reduced long-term mortality compared to medical management in adjusted analysis (OR 0.37, 95%CI 0.16-0.88, p = 0.03). CONCLUSIONS: PPMI and iCAD in patients undergoing TAVR are common. PPMI is associated with older generation valves and higher LVEF rather than traditional cardiovascular risk factors. In our study, PPMI was not associated with long-term mortality. However, in patients with iCAD, PCI was associated with reduced long-term mortality compared to medical management.

Sex differences in treatment and outcomes of patients with in-hospital ST-elevation myocardial infarction.

BACKGROUND AND HYPOTHESIS: Two cohorts face high mortality after ST-elevation myocardial infarction (STEMI): females and patients with in-hospital STEMI. The aim of this study was to evaluate sex differences in ischemic times and outcomes of in-hospital STEMI patients. METHODS: Consecutive STEMI patients treated with percutaneous coronary intervention (PCI) were prospectively recruited from 30 hospitals into the Victorian Cardiac Outcomes Registry (2013-2018). Sex discrepancies within in-hospital STEMIs were compared with out-of-hospital STEMIs. The primary endpoint was 12-month all-cause mortality. Secondary endpoints included symptom-to-device (STD) time and 30-day major adverse cardiovascular events (MACE). To investigate the relationship between sex and 12-month mortality for in-hospital versus out-of-hospital STEMIs, an interaction analysis was included in the multivariable models. RESULTS: A total of 7493 STEMI patients underwent PCI of which 494 (6.6%) occurred in-hospital. In-hospital versus out-of-hospital STEMIs comprised 31.9% and 19.9% females, respectively. Female in-hospital STEMIs were older (69.5 vs. 65.9 years, p = .003) with longer adjusted geometric mean STD times (104.6 vs. 94.3 min, p < .001) than men. Female versus male in-hospital STEMIs had no difference in 12-month mortality (27.1% vs. 20.3%, p = .92) and MACE (22.8% vs. 19.3%, p = .87). Female sex was not independently associated with 12-month mortality for in-hospital STEMIs which was consistent across the STEMI cohort (OR: 1.26, 95% CI: 0.94-1.70, p = .13). CONCLUSIONS: In-hospital STEMIs are more frequent in females relative to out-of-hospital STEMIs. Despite already being under medical care, females with in-hospital STEMIs experienced a 10-min mean excess in STD time compared with males, after adjustment for confounders. Adjusted 12-month mortality and MACE were similar to males.

Sex disparity in secondary prevention pharmacotherapy and clinical outcomes following acute coronary syndrome.

AIMS: We sought to investigate if sex disparity exists for secondary prevention pharmacotherapy following acute coronary syndrome (ACS) and impact on long-term clinical outcomes. METHODS AND RESULTS: We analysed data on medical management 30-day post-percutaneous coronary intervention (PCI) for ACS in 20 976 patients within the multicentre Melbourne Interventional Group registry (2005-2017). Optimal medical therapy (OMT) was defined as five guideline-recommended medications, near-optimal medical therapy (NMT) as four medications, sub-optimal medical therapy (SMT) as ≤3 medications. Overall, 65% of patients received OMT, 27% NMT and 8% SMT. Mean age was 64 ± 12 years; 24% (4931) were female. Women were older (68 ± 12 vs. 62 ± 12 years) and had more comorbidities. Women were less likely to receive OMT (61% vs. 66%) and more likely to receive SMT (10% vs. 8%) compared to men, P < 0.001. On long-term follow-up (median 5 years, interquartile range 2-8 years), women had higher unadjusted mortality (20% vs. 13%, P < 0.001). However, after adjusting for medical therapy and baseline risk, women had lower long-term mortality [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.79-0.98; P = 0.02]. NMT (HR 1.17, 95% CI 1.05-1.31; P = 0.004) and SMT (HR 1.79, 95% CI 1.55-2.07; P < 0.001) were found to be independent predictors of long-term mortality. CONCLUSION: Women are less likely to be prescribed optimal secondary prevention medications following PCI for ACS. Lower adjusted long-term mortality amongst women suggests that as well as baseline differences between gender, optimization of secondary prevention medical therapy amongst women can lead to improved outcomes. This highlights the need to focus on minimizing the gap in secondary prevention pharmacotherapy between sexes following ACS.

Assessment of Pretreatment With Oral P2Y12 Inhibitors and Cardiovascular and Bleeding Outcomes in Patients With Non-ST Elevation Acute Coronary Syndromes: A Systematic Review and Meta-analysis.

Importance: The practice of pretreatment with oral P2Y12 inhibitors in non-ST elevation acute coronary syndromes (NSTEACS) remains common; however, its association with improved cardiovascular outcomes is unclear. Objective: To assess the association between oral P2Y12 inhibitor pretreatment and cardiovascular and bleeding outcomes in patients with NSTEACS. Data Sources: On March 20, 2021, PubMed, MEDLINE, Embase, Scopus, Web of Science, Science Direct, clinicaltrials.gov, and the Cochrane Central Register for Controlled Trials were searched from database inception. Study Selection: Randomized clinical trials of patients with NSTEACS randomized to either oral P2Y12 inhibitor pretreatment (defined as prior to angiography) or no pretreatment (defined as following angiography, once coronary anatomy was known) among patients undergoing an invasive strategy. Data Extraction and Synthesis: This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data on publication year, sample size, clinical characteristics, revascularization strategy, P2Y12 inhibitor type and dosage, time from pretreatment to angiography, and end point data were independently extracted by 2 authors. A random-effects model was used, including stratification by (1) P2Y12 inhibitor type, (2) revascularization strategy, and (3) access site. Main Outcomes and Measures: The primary end point was 30-day major adverse cardiac events (MACEs). Secondary end points were 30-day myocardial infarction (MI) and cardiovascular death. The primary safety end point was 30-day major bleeding (defined according to individual studies). Results: A total of 7 trials randomizing 13 226 patients to either pretreatment (6603 patients) or no pretreatment (6623 patients) were included. The mean age of patients was 64 years and 3598 (27.2%) were female individuals. Indication for P2Y12 inhibitors was non-ST elevation myocardial infarction in 7430 patients (61.7%), radial access was used in 4295 (32.6%), and 10 945 (82.8%) underwent percutaneous coronary intervention. Pretreatment was not associated with a reduction in 30-day MACE (odds ratio [OR], 0.95; 95% CI, 0.78-1.15; I2 = 28%), 30-day MI (OR, 0.90; 95% CI, 0.72-1.12; I2 = 19%), or 30-day cardiovascular death (OR, 0.79; 95% CI, 0.49-1.27; I2 = 0%). The risk of 30-day major bleeding was increased among patients who underwent pretreatment (OR, 1.51; 95% CI, 1.16-1.97; I2 = 41%). The number needed to harm to bring about 1 major bleeding event with oral P2Y12 inhibitor pretreatment was 63 patients. Conclusions and Relevance: In this study, pretreatment with oral P2Y12 inhibitors among patients with NSTEACS prior to angiography, compared with treatment once coronary anatomy is known, was associated with increased bleeding risk and no difference in cardiovascular outcomes. Routine pretreatment with oral P2Y12 inhibitors in patients with NSTEACS receiving an early invasive strategy is not supported by this study.

Sex Differences in Prehospital Delays in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Background Women with ST-segment-elevation myocardial infarction experience delays in reperfusion compared with men with little data on each time component from symptom onset to reperfusion. This study analyzed sex discrepancies in patient delays, prehospital system delays, and hospital delays. Methods and Results Consecutive patients with ST-segment-elevation myocardial infarction treated with percutaneous coronary intervention across 30 hospitals in the Victorian Cardiac Outcomes Registry (2013-2018) were analyzed. Data from the Ambulance Victoria Data warehouse were used to perform linkage to the Victorian Cardiac Outcomes Registry for all patients transported via emergency medical services (EMS). The primary end point was EMS call-to-door time (prehospital system delay). Secondary end points included symptom-to-EMS call time (patient delay), door-to-device time (hospital delay), 30-day mortality, major adverse cardiovascular events, and major bleeding. End points were analyzed according to sex and adjusted for age, comorbidities, cardiogenic shock, cardiac arrest, and symptom onset time. A total of 6330 (21% women) patients with ST-segment-elevation myocardial infarction were transported by EMS. Compared with men, women had longer adjusted geometric mean symptom-to-EMS call times (47.0 versus 44.0 minutes; P<0.001), EMS call-to-door times (58.1 versus 55.7 minutes; P<0.001), and door-to-device times (58.5 versus 54.9 minutes; P=0.006). Compared with men, women had higher 30-day mortality (odds ratio [OR], 1.38; 95% CI, 1.06-1.79; P=0.02) and major bleeding (OR, 1.54; 95% CI, 1.08-2.20; P=0.02). Conclusions Female patients with ST-segment-elevation myocardial infarction experienced excess delays in patient delays, prehospital system delays, and hospital delays, even after adjustment for confounders. Prehospital system and hospital delays resulted in an adjusted excess delay of 10 minutes compared with men.

Impact of Gender on Transcatheter Aortic Valve Implantation Outcomes.

Previous studies indicate that women who underwentwho underwent transcatheter aortic valve implantation (TAVI) have poorer 30-day outcomes compared with men. However, the effect of gender as a prognostic factor for long-term outcomes following TAVI remains unclear. Between 2008 and 2018, all patients (n = 683) who underwent TAVI in 2 centres in Melbourne, Australia were prospectively included in a registry. The primary end-point was long-term mortality. The secondary end points were Valve Academic Research Consortium-2 (VARC-2) in-hospital complications and mortality at 30-days and 1-year. Of 683 patients, 328 (48%) were women. Women had a higher mean STS-PROM score (5.2 ± 3.1 vs 4.6 ± 3.5, p < 0.001) but less co-morbidities than men. Women had a significantly higher in-hospital bleeding rates (3.3% vs 1.0%, Odds Ratio 4.21, 95% confidence interval [CI] 1.16 to15.25, p = 0.027) and higher 30-day mortality (2.4% vs 0.3%, hazard ratio [HR] 8.75, 95% CI 1.09 to 69.6, p = 0.040) than men. Other VARC-2 outcomes were similar between genders. Overall mortality rate was 36% (246) over a median follow up of 2.7 (interquartile rang [IQR] 1.7 to 4.2) years. Median time to death was 5.3 (95% CI 4.7 to 5.7) years. One-year mortality was similar between genders (8.3% vs 7.8%), as was long-term mortality (HR = 0.91, 95% CI 0.71 to 1.17, p = 0.38). On multivariable analysis, female gender was an independent predictor for 1-year mortality (HR = 2.33, 95% CI 1.11 to 4.92, p = 0.026), but not long-term mortality (HR = 0.78, 95% CI 0.54 to 1.14, p = 0.20). In the women only cohort, STS-PROM was the only independent predictor of long-term mortality (HR 1.88, 95% CI 1.42 to 2.48, p < 0.001). In conclusion, women had higher rates of peri-procedural major bleeding and 30-day mortality following TAVI. However, long-term outcomes were similar between genders.