The cost-effectiveness of semaglutide in reducing cardiovascular risk among people with overweight and obesity and existing cardiovascular disease, but without diabetes.

BACKGROUND AND AIMS: The Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial demonstrated significant reductions in cardiovascular outcomes in people with cardiovascular disease (CVD) and overweight or obesity (but without diabetes). However, the cost of the medication has raised concerns about its financial viability and accessibility within healthcare systems. This study explored whether use of semaglutide for the secondary prevention of CVD in overweight or obesity is cost-effective from the Australian healthcare perspective. METHODS: A Markov model was developed based on the SELECT trial to model the clinical outcomes and costs of a hypothetical population treated with semaglutide versus placebo, in addition to standard care, and followed up over 20 years. With each annual cycle, subjects were at risk of having non-fatal CVD events or dying. Model inputs were derived from SELECT and published literature. Costs were obtained from Australian sources. All outcomes were discounted by 5% annually. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. RESULTS: With an annual estimated cost of semaglutide of A${\$}$4175, the model resulted in ICERs of A${\$}$99 853 (US${\$}$143 504; £40 873) per YoLS and A${\$}$96 055 (US${\$}$138 046; £39 318) per QALY gained. CONCLUSIONS: Assuming a willingness-to-pay threshold of A${\$}$50 000, semaglutide is not considered cost-effective at the current price. A price of ≤ A${\$}$2000 per year or more targeted use in high-risk patients would be needed for it to be considered cost-effective in the Australian setting.

Routine Protamine Administration for Bleeding in Transcatheter Aortic Valve Implantation: The ACE-PROTAVI Randomized Clinical Trial.

Importance: Vascular complications after transfemoral transcatheter aortic valve implantation (TAVI) remain an important cause of procedure-related morbidity. Routine reversal of anticoagulation with protamine at the conclusion of transfemoral TAVI could reduce complications, but data remain scarce. Objective: To evaluate the efficacy and safety of routine protamine administration after transfemoral TAVI. Design, Setting, and Participants: The ACE-PROTAVI trial was an investigator-initiated, double-blind, placebo-controlled randomized clinical trial performed at 3 Australian hospitals between December 2021 and June 2023 with a 1-year follow-up period. All patients accepted for transfemoral TAVI by a multidisciplinary heart team were eligible for enrollment. Interventions: Eligible patients were randomized 1:1 between routine protamine administration and placebo. Main Outcomes and Measures: The coprimary outcomes were the rate of hemostasis success and time to hemostasis (TTH), presented as categorical variables and compared with a χ2 test or as continuous variables as mean (SD) or median (IQR), depending on distribution. The major secondary outcome was a composite of all-cause death, major and minor bleeding complications, and major and minor vascular complications after 30 days, reported in odds ratios (ORs) with 95% CIs and P values. Results: The study population consisted of 410 patients: 199 patients in the protamine group and 211 in the placebo group. The median (IQR) patient age in the protamine group was 82 (77-85) years, and 68 of 199 patients receiving protamine (34.2%) were female. The median (IQR) patient age in the placebo group was 80 (75-85) years, and 89 of 211 patients receiving the placebo (42.2%) were female. Patients receiving up-front protamine administration had a higher rate of hemostasis success (188 of 192 patients [97.9%]) than patients in the placebo group (186 of 203 patients [91.6%]; absolute risk difference, 6.3%; 95% CI, 2.0%-10.6%; P = .006); in addition, patients receiving up-front protamine had a shorter median (IQR) TTH (181 [120-420] seconds vs 279 [122-600] seconds; P = .002). Routine protamine administration resulted in a reduced risk of the composite outcome in the protamine group (10 of 192 [5.2%]) vs the placebo group (26 of 203 [12.8%]; OR, 0.37; 95% CI, 0.1-0.8; P = .01). This difference was predominantly driven by the difference in the prevalence of minor vascular complications. There were no adverse events associated with protamine use. Conclusions and Relevance: In the ACE-PROTAVI randomized clinical trial, routine administration of protamine increased the rate of hemostasis success and decreased TTH. The beneficial effect of protamine was reflected in a reduction in minor vascular complications, procedural time, and postprocedural hospital stay duration in patients receiving routine protamine compared with patients receiving placebo. Trial Registration: anzctr.org.au Identifier: ACTRN12621001261808.

Incidence and predictors of vascular complications following transcatheter aortic valve implantation: A comparison of the MANTA and suture-based vascular closure devices.

BACKGROUND: Vascular complications post-transcatheter aortic valve implantation (TAVI) are common. Recent data regarding predictors of vascular complications are limited, particularly comparing newer plug-based devices versus traditional suture-based vascular closure devices (VCD). AIM: The primary objective was to identify characteristics that predict a higher risk of vascular complications in TAVI patients, as judged by the VARC-3 criteria, specifically comparing risk factors between suture-based vs MANTA device closure. METHODS: Retrospective analysis of patients who underwent TAVI between December 2019 and September 2023 was performed. Logistic regression and propensity score matching was performed to ascertain risk factors for vascular complications post-TAVI. RESULTS: Of the 1763 patients, there were 106 vascular complications (6%). There was a nonsignificant increased complication rate in MANTA vs suture-based device closure (8.3% vs 5.3%, p = 0.064). Among these, the most common complications were VCD failure (23%), pseudoaneurysm (20%) and arterial dissection (19%). Obesity (p = 0.021), anemia (p = 0.039) and MANTA device use (p = 0.027) were predictors of vascular complications. Within the MANTA cohort, novel oral anticoagulant (NOAC) use was predictive of vascular complications (p = 0.002). Among suture-based devices, obesity (p = 0.037) and anaemia (p = 0.017) were significant predictors. A propensity matched analysis derived 90 pairs of patients matched for age, gender, diabetes, peripheral arterial disease, NOAC use, anemia and obesity, identifying an average treatment effect of 0.039 (p = 0.04) when MANTA device closure was performed. CONCLUSION: Vascular complications in TAVI remain common. Identifying predictors such as MANTA device closure, obesity, anemia, and baseline NOAC use will allow for improved risk stratification and appropriate VCD selection in patients undergoing TAVI.

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.

Artificial neural networks for ECG interpretation in acute coronary syndrome: A scoping review.

INTRODUCTION: The electrocardiogram (ECG) is a crucial diagnostic tool in the Emergency Department (ED) for assessing patients with Acute Coronary Syndrome (ACS). Despite its widespread use, the ECG has limitations, including low sensitivity of the STEMI criteria to detect Acute Coronary Occlusion (ACO) and poor inter-rater reliability. Emerging ECG features beyond the traditional STEMI criteria show promise in improving early ACO diagnosis, but complexity hinders widespread adoption. The potential integration of Artificial Neural Networks (ANN) holds promise for enhancing diagnostic accuracy and addressing reliability issues in ECG interpretation for ACO symptoms. METHODS: Ovid MEDLINE, CINAHL, EMBASE, Cochrane, PubMed and Scopus were searched from inception through to 8th of December 2023. A thorough search of the grey literature and reference lists of relevant articles was also performed to identify additional studies. Articles were included if they reported the use of ANN for ECG interpretation of Acute Coronary Syndrome in the Emergency Department patients. RESULTS: The search yielded a total of 244 articles. After removing duplicates and excluding non-relevant articles, 14 remained for analysis. There was significant heterogeneity in the types of ANN models used and the outcomes assessed, making direct comparisons challenging. Nevertheless, ANN appeared to demonstrate higher accuracy than physician interpreters for the evaluated outcomes and this proved independent of both specialty and years of experience. CONCLUSIONS: The interpretation of ECGs in patients with suspected ACS using ANN appears to be accurate and potentially superior when compared to human interpreters and computerised algorithms. This appears consistent across various ANN models and outcome variables. Future investigations should emphasise ANN interpretation of ECGs in patients with ACO, where rapid and accurate diagnosis can significantly benefit patients through timely access to reperfusion therapies.

Prevalence and outcomes of patients with SMuRF-less acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: There is increasing awareness that patients without standard modifiable risk factors (SMuRFs; diabetes, hypercholesterolaemia, hypertension and smoking) may represent a unique subset of patients with acute coronary syndrome (ACS). We aimed to investigate the prevalence and outcomes of patients with SMuRF-less ACS undergoing percutaneous coronary intervention (PCI) compared with those with SMuRFs. METHODS: We analysed data from the Melbourne Interventional Group PCI Registry. Patients with coronary artery disease were excluded. The primary outcome was 30-day mortality. Secondary outcomes included in-hospital and 30-day events. Long-term mortality was investigated using Cox-proportional hazards regression. RESULTS: From 1 January 2005 to 31 December 2020, 2727/18 988 (14.4%) patients were SMuRF less, with the proportion increasing over time. Mean age was similar for patients with and without SMuRFs (63 years), and fewer females were SMuRF-less (19.8% vs 25.4%, p<0.001). SMuRF-less patients were more likely to present with cardiac arrest (6.6% vs 3.9%, p<0.001) and ST-elevation myocardial infarction (59.1% vs 50.8%, p<0.001) and were more likely to experience postprocedural cardiogenic shock (4.5% vs 3.6%, p=0.019) and arrhythmia (11.2% vs 9.9%, p=0.029). At 30 days, mortality, myocardial infarction, revascularisation and major adverse cardiac and cerebrovascular events did not differ between the groups. During median follow-up of 7 years, SMuRF-less patients had an adjusted 13% decreased rate of mortality (HR 0.87 (95% CI 0.78 to 0.97)). CONCLUSIONS: The proportion of SMuRF-less patients increased over time. Presentation was more often a devastating cardiac event compared with those with SMuRFs. No difference in 30-day outcomes was observed and SMuRF-less patients had lower hazard for long-term mortality.

Ten-Year Risk Equations for Incident Heart Failure in Established Atherosclerotic Cardiovascular Disease Populations.

BACKGROUND: Ten-year risk equations for incident heart failure (HF) are available for the general population, but not for patients with established atherosclerotic cardiovascular disease (ASCVD), which is highly prevalent in HF cohorts. This study aimed to develop and validate 10-year risk equations for incident HF in patients with known ASCVD. METHODS AND RESULTS: Ten-year risk equations for incident HF were developed using the United Kingdom Biobank cohort (recruitment 2006-2010) including participants with established ASCVD but free from HF at baseline. Model performance was validated using the Australian Baker Heart and Diabetes Institute Biobank cohort (recruitment 2000-2011) and compared with the performance of general population risk models. Incident HF occurred in 13.7% of the development cohort (n=31 446, median 63 years, 35% women, follow-up 10.7±2.7 years) and in 21.3% of the validation cohort (n=1659, median age 65 years, 25% women, follow-up 9.4±3.7 years). Predictors of HF included in the sex-specific models were age, body mass index, systolic blood pressure (treated or untreated), glucose (treated or untreated), cholesterol, smoking status, QRS duration, kidney disease, myocardial infarction, and atrial fibrillation. ASCVD-HF equations had good discrimination and calibration in development and validation cohorts, with superior performance to general population risk equations. CONCLUSIONS: ASCVD-specific 10-year risk equations for HF outperform general population risk models in individuals with established ASCVD. The ASCVD-HF equations can be calculated from readily available clinical data and could facilitate screening and preventative treatment decisions in this high-risk group.

Hyperlactataemia is a marker of reduced exercise capacity in heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is associated with an array of central and peripheral haemodynamic and metabolic changes. The exact pathogenesis of exercise limitation in HFpEF remains uncertain. Our aim was to compare lactate accumulation and central haemodynamic responses to exercise in patients with HFpEF, non-cardiac dyspnoea (NCD), and healthy volunteers. METHODS AND RESULTS: Right heart catheterization with mixed venous blood gas and lactate measurements was performed at rest and during symptom-limited supine exercise. Multivariable analyses were conducted to determine the relationship between haemodynamic and biochemical parameters and their association with exercise capacity. Of 362 subjects, 198 (55%) had HFpEF, 103 (28%) had NCD, and 61 (17%) were healthy volunteers. This included 139 (70%) females with HFpEF, 77 (75%) in NCD (P = 0.41 HFpEF vs. NCD), and 31 (51%) in healthy volunteers (P < 0.001 HFpEF vs. volunteers). The median age was 71 (65, 75) years in HFpEF, 66 (57, 72) years in NCD, and 49 (38, 65) years in healthy volunteers (HFpEF vs. NCD or volunteer, both P < 0.001). Peak workload was lower in HFpEF compared with healthy volunteers [52 W (interquartile range 31-73), 150 W (125-175), P < 0.001], but not NCD [53 W (33, 75), P = 0.85]. Exercise lactate indexed to workload was higher in HFpEF at 0.08 mmol/L/W (0.05-0.11), 0.06 mmol/L/W (0.05-0.08; P = 0.016) in NCD, and 0.04 mmol/L/W (0.03-0.05; P < 0.001) in volunteers. Exercise cardiac index was 4.5 L/min/m2 (3.7-5.5) in HFpEF, 5.2 L/min/m2 (4.3-6.2; P < 0.001) in NCD, and 9.1 L/min/m2 (8.0-9.9; P < 0.001) in volunteers. Oxygen delivery in HFpEF was lower at 1553 mL/min (1175-1986) vs. 1758 mL/min (1361-2282; P = 0.024) in NCD and 3117 mL/min (2667-3502; P < 0.001) in the volunteer group during exercise. Predictors of higher exercise lactate levels in HFpEF following adjustment included female sex and chronic kidney disease (both P < 0.001). CONCLUSIONS: HFpEF is associated with reduced exercise capacity secondary to both central and peripheral factors that alter oxygen utilization. This results in hyperlactataemia. In HFpEF, plasma lactate responses to exercise may be a marker of haemodynamic and cardiometabolic derangements and represent an important target for future potential therapies.

Cardiac Substrate Utilization and Relationship to Invasive Exercise Hemodynamic Parameters in HFpEF.

The authors conducted transcardiac blood sampling in healthy subjects and subjects with heart failure with preserved ejection fraction (HFpEF) to compare cardiac metabolite and lipid substrate use. We demonstrate that fatty acids are less used by HFpEF hearts and that lipid extraction is influenced by hemodynamic factors including pulmonary pressures and cardiac index. The release of many products of protein catabolism is apparent in HFpEF compared to healthy myocardium. In subgroup analyses, differences in energy substrate use between female and male hearts were identified.

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.

Incidence, Predictors, and Outcomes of Nonhome Discharge Following Transcatheter Aortic Valve Implantation: A Multicenter Australian Experience-The NHD TAVI Study.

Patients who undergo transcatheter aortic valve implantation (TAVI) commonly experience nonhome discharge (NHD), a phenomenon associated with increased health care expenditure and possibly poorer outcomes. Despite its clinical relevance in TAVI, the incidence and predictors of NHD and its impact on the quality of life remain poorly characterized. Also unknown is the proportion of patients who undergo TAVI that require long-term residential care after initial NHD. Therefore, we aimed to address these questions using a large, multicenter Australian cohort. A total of 2,229 patients who underwent TAVI from 2010 to 2023 included in the Alfred-Cabrini-Epworth TAVI Registry were analyzed. The median age was 82 (interquartile range 78 to 86) years and 41% were women. A total of 257 patients (12%) were not discharged home after TAVI, with the incidence falling over time (R2 = 0.636, p <0.001). A multivariable logistic regression model for NHD prediction was developed with excellent calibration and discrimination (C-statistic = 0.835). The independent predictors of NHD were postprocedural stroke (adjusted odds ratio [aOR] 11.05), procedure at a private hospital (aOR 3.01), living alone (aOR 2.35), vascular access site complications (aOR 2.09), frailty (aOR 1.89), age >80 years (aOR 1.82), hypoalbuminemia (aOR 1.76), New York Heart Association III to IV (aOR 1.74), and hospital length of stay (aOR 1.13) (all p <0.05). NHD was not associated with mortality at 30 days and <1% of all patients required longer-term residential care. In conclusion, although common after TAVI, NHD does not predict short-term mortality, most patients successfully return home within 30 days, and when used appropriately, NHD may serve as a brief and effective method of optimizing functional status without compromising long-term independence.

Predictors of pacemaker requirement in patients receiving implantable loop recorders for unexplained syncope: A systematic review and meta-analysis.

BACKGROUND: Implantable loop recorders (ILRs) are increasingly used to evaluate patients with unexplained syncope. Identification of all predictors of bradycardic syncope and consequent permanent pacemaker (PPM) insertion is of substantial clinical interest as patients in the highest risk category may benefit from upfront pacemaker insertion. OBJECTIVE: We performed a systematic review and meta-analysis to identify risk predictors for PPM insertion in ILR recipients with unexplained syncope. METHODS: An electronic database search (MEDLINE, Embase, Scopus, Cochrane) was performed in June 2023. Studies evaluating ILR recipients with unexplained syncope and recording risk factors for eventual PPM insertion were included. A random effects model was used to calculate the pooled odds ratio (OR) for clinical and electrocardiographic characteristics with respect to future PPM requirement. RESULTS: Eight studies evaluating 1007 ILR recipients were included; 268 patients (26.6%) underwent PPM insertion during study follow-up. PPM recipients were older (mean age, 70.2 ± 15.4 years vs 61.6 ± 19.7 years; P < .001). PR prolongation on baseline electrocardiography was a significant predictor of PPM requirement (pooled OR, 2.91; 95% confidence interval, 1.63-5.20). The presence of distal conduction system disease, encompassing any bundle branch or fascicular block, yielded a pooled OR of 2.88 for PPM insertion (95% confidence interval, 1.53-5.41). Injurious syncope and lack of syncopal prodrome were not significant predictors of PPM insertion. Sinus node dysfunction accounted for 62% of PPM insertions, whereas atrioventricular block accounted for 26%. CONCLUSION: Approximately one-quarter of ILR recipients for unexplained syncope require eventual PPM insertion. Advancing age, PR prolongation, and distal conduction disease are the strongest predictors for PPM requirement.

The Impact of Diabetes on Haemodynamic and Cardiometabolic Responses in Heart Failure With Preserved Ejection Fraction.

AIMS: Heart failure with preserved ejection (HFpEF) and diabetes mellitus (DM) commonly co-exist. However, it is unclear if DM modifies the haemodynamic and cardiometabolic phenotype in patients with HFpEF. We aimed to interrogate the haemodynamic and cardiometabolic effects of DM in HFpEF. METHODS: We compared the haemodynamic and metabolic profiles of non-DM patients and patients with DM-HFpEF at rest and during exercise using right heart catheterisation and mixed venous blood gas analysis. RESULTS: Of 181 patients with HFpEF, 37 (20%) had DM. Patients with DM displayed a more adverse exercise haemodynamic response vs HFpEF alone (mean pulmonary arterial pressure: 47 mmHg [interquartile range {IQR} 42-55] vs 42 [38-47], p<0.001; workload indexed pulmonary capillary wedge pressure indexed: 0.80 mmHg/W [0.44-1.23] vs 0.57 [0.43-1.01], p=0.047). HFpEF-DM patients had a lower mixed venous oxygen saturation at rest (70% [IQR 66-73] vs 72 [69-75], p=0.003) and were unable to enhance O2 extraction to the same extent (Δ-28% [-33 to -15] vs -29 [-36 to -21], p=0.029), this occurred at a 22% lower median workload. Resting mixed venous lactate levels were higher in those with DM (1.5 mmol/L [IQR 1.1-1.9] vs 1 [0.9-1.3], p<0.001), and during exercise indexed to workload (0.09 mmol/L/W [0.06-0.13] vs 0.08 [0.05-0.11], p=0.018). CONCLUSION: Concurrent diabetes and HFpEF was associated with greater metabolic responses at rest, with enhanced wedge driven pulmonary hypertension and relative lactataemia during exercise without appropriate augmentation of oxygen consumption.

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.

Early Discharge to Clinic-Based Therapy of Patients Presenting With Decompensated Heart Failure (EDICT-HF): Study Protocol for a Multi-Centre Randomised Controlled Trial.

BACKGROUND: Acute decompensated heart failure involves a high rate of mortality and complications. Management typically involves a multi-day hospital admission. However, patients often lose part of their function with each successive admission, and are at a high risk for hospital-associated complications such as nosocomial infection. This study aims to determine the safety and efficacy of the management of patients presenting with acute decompensated heart failure to clinic-based therapy vs usual inpatient care using a reproducible management pathway. METHOD: An investigator-initiated, prospective, non-inferiority, 1:1 randomised-controlled trial, stratified by left ventricular ejection fraction including 460 patients with a minimum follow-up of 7 days. This is a multi-centre study to be performed in centres across Victoria, Australia. Participants will be patients with either heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), admitted for acute decompensation of heart failure. INTERVENTION: Early discharge to an outpatient-based Heart Failure Rapid Access Clinical Review (RACER) in addition to frequent medical/nursing at-home review for patients admitted with decompensated heart failure. RESULTS: The primary endpoint will be a non-inferiority assessment of re-hospitalisation at 30 days. Secondary outcomes include superiority assessment of hospitalisation at 30 days, a composite clinical endpoint of major adverse cardiac and cerebrovascular event (MACCE), hospital re-admission or mortality at 3 months, achievement of guideline-directed medical therapy, patient assessment of symptoms (visual-analogue scale quantified as area under curve and Kansas City Cardiomyopathy Questionnaire-12 [KCCQ-12]), attendance at 3-month outpatient follow-up, number of bed stays/clinics attended, proportion of patients free from congestion, change in serum creatinine level, treatment for electrolyte disturbances, time to transition from intravenous to oral diuretics, and health economics analysis (cost-benefit analysis, cost-utility analysis, incremental cost-effectiveness ratio). CONCLUSIONS: The Early Discharge to Clinic-Based Therapy of Patients Presenting with Decompensated Heart Failure (EDICT-HF) trial will help determine whether earlier discharge to out-of-hospital care is non-inferior to the usual practice of inpatient care, in patients with heart failure admitted to hospital for acute decompensation, as an alternative model of care.

Stroke reduction by cerebral embolic protection devices in transcatheter aortic valve implantation: a systematic review and Bayesian meta-analysis.

OBJECTIVES: The use of cerebral embolic protection (CEP) during transcatheter aortic valve implantation (TAVI) has been studied in several randomised trials. We aimed to perform a systematic review and Bayesian meta-analysis of randomised CEP trials, focusing on a clinically relevant reduction in disabling stroke. METHODS: A systematic search was applied to three electronic databases, including trials that randomised TAVI patients to CEP versus standard treatment. The primary outcome was the risk of disabling stroke. Outcomes were presented as relative risk (RR), absolute risk differences (ARDs), numbers needed to treat (NNTs) and the 95% credible intervals (CrIs). The minimal clinically important difference was determined at 1.1% ARD, per expert consensus (NNT 91). The principal Bayesian meta-analysis was performed under a vague prior, and secondary analyses were performed under two informed literature-based priors. RESULTS: Seven randomised studies were included for meta-analysis (n=3996: CEP n=2126, control n=1870). Under a vague prior, the estimated median RR of CEP use for disabling stroke was 0.56 (95% CrI 0.28 to 1.19, derived ARD 0.56% and NNT 179, I2=0%). Although the estimated posterior probability of any benefit was 94.4%, the probability of a clinically relevant effect was 0-0.1% under the vague and informed literature-based priors. Results were robust across multiple sensitivity analyses. CONCLUSION: There is a high probability of a beneficial CEP treatment effect, but this is unlikely to be clinically relevant. These findings suggest that future trials should focus on identifying TAVI patients with an increased baseline risk of stroke, and on the development of new generation devices. PROSPERO REGISTRATION NUMBER: CRD42023407006.

Differences in predictors of incident heart failure according to atherosclerotic cardiovascular disease status.

AIMS: Heart failure (HF) is a common cause of morbidity and mortality, related to a broad range of sociodemographic, lifestyle, cardiometabolic, and comorbidity risk factors, which may differ according to the presence of atherosclerotic cardiovascular disease (ASCVD). We assessed the association between incident HF with baseline status across these domains, overall and separated according to ASCVD status. METHODS AND RESULTS: We included 5758 participants from the Baker Biobank cohort without HF at baseline enrolled between January 2000 and December 2011. The primary endpoint was incident HF, defined as hospital admission or HF-related death, determined through linkage with state-wide administrative databases (median follow-up 12.2 years). Regression models were fitted adjusted for sociodemographic variables, alcohol intake, smoking status, measures of adiposity, cardiometabolic profile measures, and individual comorbidities. During 65 987 person-years (median age 59 years, 38% women), incident HF occurred among 784 participants (13.6%) overall. Rates of incident HF were higher among patients with ASCVD (624/1929, 32.4%) compared with those without ASCVD (160/3829, 4.2%). Incident HF was associated with age, socio-economic status, alcohol intake, smoking status, body mass index (BMI), waist circumference, waist-hip ratio, systolic blood pressure (SBP), and low- and high-density lipoprotein cholesterol (LDL-C and HDL-C), with non-linear relationships observed for age, alcohol intake, BMI, waist circumference, waist-hip ratio, SBP, LDL-C, and HDL-C. Risk factors for incident HF were largely consistent regardless of ASCVD status, although diabetes status had a greater association with incident HF among patients without ASCVD. CONCLUSIONS: Incident HF is associated with a broad range of baseline sociodemographic, lifestyle, cardiometabolic, and comorbidity factors, which are mostly consistent regardless of ASCVD status. These data could be useful in efforts towards developing risk prediction models that can be used in patients with ASCVD.