Restoring microvascular circulation with diagnostic ultrasound and contrast agent: Rationale and Design of the REDUCE trial.

OBJECTIVES: This study aims to evaluate the efficacy and cost-effectiveness of sonothrombolysis delivered pre and post primary percutaneous coronary intervention (pPCI) on infarct size assessed by cardiac MRI, in patients presenting with STEMI, when compared against sham procedure. BACKGROUND: More than a half of patients with successful pPCI have significant microvascular obstruction and residual infarction. Sonothrombolysis is a therapeutic use of ultrasound with contrast enhancement that may improve microcirculation and infarct size. The benefits and real time physiological effects of sonothrombolysis in a multicentre setting are unclear. METHODS: The REDUCE (Restoring microvascular circulation with diagnostic ultrasound and contrast agent) trial is a prospective, multicentre, patient and outcome blinded, sham-controlled trial. Patients presenting with STEMI will be randomized to one of two treatment arms, to receive either sonothrombolysis treatment or sham echocardiography before and after pPCI. This tailored design is based on preliminary pilot data from our centre, showing that sonothrombolysis can be safely delivered, without prolonging door to balloon time. Our primary endpoint will be infarct size assessed on day 4±2 on Cardiac Magnetic Resonance (CMR). Patients will be followed up for six months post pPCI to assess secondary endpoints. Sample size calculations indicate we will need 150 patients recruited in total. CONCLUSIONS: This multicentre trial will test whether sonothrombolysis delivered pre and post primary PCI can improve patient outcomes and is cost-effective, when compared with sham ultrasound delivered with primary PCI. The results from this trial may provide evidence for the utilization of sonothrombolysis as an adjunct therapy to pPCI to improve cardiovascular outcomes in STEMI. ANZ Clinical Trial Registration number: ACTRN 12620000807954.

Correlation of Noninvasive Cardiac MRI Measures of Left Ventricular Myocardial Function and Invasive Pressure-Volume Parameters in a Porcine Ischemia-Reperfusion Model.

Purpose To assess the correlation between noninvasive cardiac MRI-derived parameters with pressure-volume (PV) loop data and evaluate changes in left ventricular function after myocardial infarction (MI). Materials and Methods Sixteen adult female swine were induced with MI, with six swine used as controls and 10 receiving platelet-derived growth factor-AB (PDGF-AB). Load-independent measures of cardiac function, including slopes of end-systolic pressure-volume relationship (ESPVR) and preload recruitable stroke work (PRSW), were obtained on day 28 after MI. Cardiac MRI was performed on day 2 and day 28 after infarct. Global longitudinal strain (GLS) and global circumferential strain (GCS) were measured. Ventriculo-arterial coupling (VAC) was derived from PV loop and cardiac MRI data. Pearson correlation analysis was performed. Results GCS (r = 0.60, P = .01), left ventricular ejection fraction (LVEF) (r = 0.60, P = .01), and cardiac MRI-derived VAC (r = 0.61, P = .01) had a significant linear relationship with ESPVR. GCS (r = 0.75, P < .001) had the strongest significant linear relationship with PRSW, followed by LVEF (r = 0.67, P = .005) and cardiac MRI-derived VAC (r = 0.60, P = .01). GLS was not significantly correlated with ESPVR or PRSW. There was a linear correlation (r = 0.82, P < .001) between VAC derived from cardiac MRI and from PV loop data. GCS (-3.5% ± 2.3 vs 0.5% ± 1.4, P = .007) and cardiac MRI-derived VAC (-0.6 ± 0.6 vs 0.3 ± 0.3, P = .001) significantly improved in the animals treated with PDGF-AB 28 days after MI compared with controls. Conclusion Cardiac MRI-derived parameters of MI correlated with invasive PV measures, with GCS showing the strongest correlation. Cardiac MRI-derived measures also demonstrated utility in assessing therapeutic benefit using PDGF-AB. Keywords: Cardiac MRI, Myocardial Infarction, Pressure Volume Loop, Strain Imaging, Ventriculo-arterial Coupling Supplemental material is available for this article. © RSNA, 2024.

Coronary Flow Velocity Reserve Declines After Anthracycline Therapy in Breast Cancer Patients.

Anthracycline therapy (ANT) is associated with cancer therapy-related cardiac dysfunction. Coronary flow velocity reserve (CFVR) has shown prognostic utility in non-cancer cohorts, but no data have been obtained in a cardio-oncology setting. We investigated the acute effect of ANT on CFVR in breast cancer patients. A total of 12 female breast cancer patients undergoing ANT had pre- and post-ANT CFVR assessment. A significant decline in CFVR occurred (baseline: 2.66 ± 0.41 vs post-ANT: 2.47 ± 0.37, P = 0.016). This prospective study is the first to identify ANT-related coronary physiology changes in humans. Further studies are required to determine their clinical significance.

Le traitement par l'anthracycline est associé à une dysfonction cardiaque liée au traitement anticancéreux. La réserve de débit coronaire a démontré son utilité pronostique dans les cohortes sans cancer, mais aucune donnée n'a été obtenue dans un contexte de cardio-oncologie. Nous avons étudié l'effet aigu de l'anthracycline sur la réserve de débit coronaire chez des patientes atteintes d'un cancer du sein. La réserve de débit coronaire a été évaluée avant et après le traitement par l'anthracycline chez un total de 12 femmes atteintes d'un cancer du sein. Un déclin important de la réserve de débit coronaire est survenu (valeur initiale de 2,66 ± 0,41 par rapport à 2,47 ± 0,37 après le traitement par l'anthracycline, p = 0,016). Cette étude prospective est la première à déceler des changements dans la physiologie coronarienne liés à l'anthracycline chez les humains. D'autres études sont nécessaires pour en déterminer la portée clinique.

Comparison of Echocardiography and Multi-Planar Gated Acquisition Scans for Predicting Cancer-Treatment-Related Cardiovascular Dysfunction.

BACKGROUND: Current guidelines recommend using sequential cardiac imaging to monitor for cancer treatment-related cardiac dysfunction (CTRCD) in patients undergoing potentially cardiotoxic chemotherapy. Multiple different imaging cardiac modalities are available and there are few prospective head-to-head comparative studies to help guide treatment. OBJECTIVES: To perform an exploratory prospective cohort study of "real-world" CTRCD comparing multigated acquisition nuclear ventriculography (MUGA) at the referring cancer specialist's discretion with a novel echocardiographic strategy at an Australian tertiary hospital. METHOD: Patients were recruited from haematology and oncology outpatient clinics if they were scheduled for treatment with anthracyclines and/or trastuzumab. Patients underwent simultaneous MUGA-based cardiac imaging (conventional strategy) at a frequency according to evidenced-based guidelines in addition to researcher-conducted echocardiographic imaging. The echocardiographic imaging was performed in all patients at time points recommended by international society guidelines. Outcomes included adherence to guideline recommendations, concordance between MUGA and echocardiographic left ventricular ejection fraction (LVEF) measurements, and detection of cardiac dysfunction (defined as >5% LVEF decrement from baseline by three-dimensional [3D]-LVEF). A secondary end point was accuracy of global longitudinal strain in predicting cardiac dysfunction. RESULTS: In total, 35 patients were recruited, including 15 with breast cancer, 19 with haematological malignancy, and one with gastric cancer. MUGA and echocardiographic LVEF measurements correlated poorly with limits of agreement of 30% between 3D-LVEF and MUGA-LVEF and 37% for 3D-LVEF and MUGA-LVEF. Only one case (2.9%) of CTRCD was diagnosed by MUGA, compared with 12 (34.2%) cases by echocardiography. Four (4) patients had >10% decrement in 3D-LVEF that was not detected by MUGA. Global longitudinal strain at 2 months displayed significant ability to predict CTRCD (area under the curve, 0.75, 95% confidence interval, 0.55-0.94). CONCLUSIONS: The MUGA correlates poorly with echocardiographic assessment with substantial discrepancy between MUGA and echocardiography in CTRCD diagnosis. Echocardiographic and MUGA imaging strategies should not be considered equivalent for imaging cancer patients, and a single imaging modality should ideally be used per patient to prevent misdiagnosis by inter-modality variation These findings should be considered hypothesis-generating and require confirmation with larger studies.

The value of right ventricular to pulmonary arterial coupling in the critically ill: a National Echocardiography Database of Australia (NEDA) substudy.

BACKGROUND: Right ventricular (RV) function is tightly coupled to afterload, yet echocardiographic indices of RV function are frequently assessed in isolation. Normalizing RV function for afterload (RV-PA coupling) using a simplified ratio of tricuspid annular plane systolic excursion (TAPSE)/ tricuspid regurgitant velocity (TRV) could help to identify RV decompensation and improve risk stratification in critically ill patients. This is the first study to explore the distribution of TAPSE/TRV ratio and its prognostic relevance in a large general critical care cohort. METHODS: We undertook retrospective analysis of echocardiographic, clinical, and mortality data of intensive care unit (ICU) patients between January 2012 and May 2017. A total of 1077 patients were included and stratified into tertile groups based on TAPSE/TRV ratio: low (< 5.9 mm.(m/s)-1), middle (≥ 5.9-8.02 mm.(m/s)-1), and high (≥ 8.03 mm.(m/s)-1). The distribution of the TAPSE/TRV ratio across ventricular function subtypes of normal, isolated left ventricular (LV), isolated RV, and biventricular dysfunction was explored. The overall prognostic relevance of the TAPSE/TRV ratio was tested, including distribution across septic, cardiovascular, respiratory, and neurological subgroups. RESULTS: Higher proportions of ventricular dysfunctions were seen in low TAPSE/TRV tertiles. TAPSE/TRV ratio is impacted by LV systolic function but to a lesser extent than RV dysfunction or biventricular dysfunction. There was a strong inverse relationship between TAPSE/TRV ratio and survival. After multivariate analysis, higher TAPSE/TRV ratios (indicating better RV-PA coupling) were independently associated with lower risk of death in ICU (HR 0.927 [0.872-0.985], p < 0.05). Kaplan-Meier analysis demonstrated higher overall survival in middle and high tertiles compared to low tertiles (log rank p < 0.0001). The prognostic relevance of TAPSE/TRV ratio was strongest in respiratory and sepsis subgroups. Patients with TAPSE/TRV < 5.9 mm (m/s)-1 had a significantly worse prognosis than those with higher TAPSE/TRV ratios. CONCLUSION: The TAPSE/TRV ratio has prognostic relevance in critically ill patients. The prognostic power may be stronger in respiratory and septic subgroups. Larger prospective studies are needed to investigate the role of TAPSE/TRV in pre-specified subgroups including its role in clinical decision-making.

Prophylaxis to Prevent Cardiotoxicity in Patients Receiving Anthracycline for Breast Cancer: A Combined Bayesian and Frequentist Network Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: The benefits in survivorship gained with anthracycline (ANT)-based chemotherapies for breast cancer are unfortunately mitigated for some patients by irreversible cardiotoxicity. Randomised controlled trials (RCTs) have explored multiple cardioprotection options, however, it remains unclear which drug is most effective in preserving left ventricular ejection fraction (LVEF). This study aimed to perform a systematic review and network meta-analysis, using Bayesian and frequentist approaches, of RCTs evaluating cardioprotective agents. METHODS: Two authors searched four databases (CENTRAL, Cochrane Reviews, MEDLINE, SCOPUS), to find RCTs evaluating cardioprotective agents. Trial populations were limited to patients with breast cancer without prior ANT exposure. The primary outcome was mean LVEF change pre and post ANT dosing. Our primary analysis utilised a Bayesian approach, while our sensitivity analysis used frequentist methodology (Prospero registration number CRD42020199580). RESULTS: From 4,007 search results, we identified 12 RCTs, with their various trial arms considered separately-nine beta-blocker (BB), two angiotensin-converting enzyme inhibitor /angiotensin receptor blockers [(AA)+BB=AABB], one AA, one spironolactone, one statin-evaluating 1,126 patients (age 50.5 years). Bayesian network meta-analysis showed no difference in LVEF preservation between AA (1.3%, 95% credible interval [-0.20, 2.9]), BB (0.77, [-0.21, 1.8]), AABB (0.84 [-1.1, 2.8]), spironolactone (0.72, [-2.3, 3.7]) or statin (0.60, [-2.4, 3.6]) when compared against placebo. However, the frequentist analysis showed benefits from using AA (mean difference, 1.32% [0.32, 2.33]) and BB (mean difference, 0.76% [0.12, 1.4]). CONCLUSIONS: There is insufficient evidence to support prophylactic cardioprotection to prevent EF reduction. However, frequentist analysis suggested that AA or BBs provide cardioprotection. Thus, for those already on other anti-hypertensives, switching to AA or BBs could be considered.

Index of Microcirculatory Resistance to predict microvascular obstruction in STEMI: A systematic review and meta-analysis.

BACKGROUND: Microvascular obstruction (MVO) is an independent predictor of adverse cardiac events after ST-elevation myocardial infarction (STEMI). The Index of Microcirculatory Resistance (IMR) may be a useful marker of MVO, which could simplify the care pathway without the need for Cardiac Magnetic Resonance (CMR). We assessed whether the IMR can predict MVO in STEMI patients. METHODS AND RESULTS: We conducted a systematic review and meta-analysis, including articles where invasive IMR was performed post primary percutaneous coronary intervention (PCI) in addition to MVO assessment with cardiac MRI. We searched PubMed, Scopus, Embase, and Cochrane databases from inception until January 2023. Baseline characteristics, coronary physiology and cardiac MRI data were extracted by two independent reviewers. The random-effects model was used to pool the data. Among 15 articles identified, nine articles (n = 728, mean age 61, 81% male) contained IMR data stratified by MVO. Patients with MVO had a mean IMR of 41.2 [95% CI 32.4-50.4], compared to 25.3 [18.3-32.2] for those without. The difference in IMR between those with and without MVO was 15.1 [9.7-20.6]. Meta-regression analyses demonstrated a linear relationship between IMR and TIMI grade (ß = 0.69 [0.13-1.26]), as well as infarct size (ß = 1.18 [0.24-2.11]) or ejection fraction at 6 months (ß = -0.18 [-0.35 to -0.01]). CONCLUSION: In STEMI, patients with MVO had 15-unit higher IMR than those without. IMR also predicts key prognostic endpoints such as infarct size, MVO, and long-term systolic function.

Silicon nanoparticles: A promising approach for control of Pseudomonas aeruginosa biofilms.

Objectives: The current study aimed to investigate the control and treatment of biofilm-producing isolates of Pseudomonas aeruginosa using silicon nanoparticles (SiNPs). Materials and Methods: Biofilm-producing isolates of P. aeruginosa were recovered from various food samples and identified through fluorescent green colony formation on selective and differential media, as well as the amplification of oprI and oprL genes. Tube methods, Congo-red agar method, and scanning electron microscopy (SEM) were used to study biofilm phenotypes. The effect of SiNPs was evaluated by broth dilution assay. Results: The biofilm assay revealed that these isolates formed biofilms on glass surfaces within 72 hr of incubation. Scanning electron micrographs showed that the biofilm communities were composed of multicellular clusters of P. aeruginosa encased in matrix material. However, these isolates were unable to form biofilms on SiNPs-coated surfaces. The results showed that the planktonic isolates of P. aeruginosa were comparatively sensitive to the antibacterial properties of SiNPs, with minimum inhibitory concentration (MIC) ranging from 100 to 200 µg/ml. Contrarily, the biofilms were found to be 500 times more tolerant to the highest concentration of SiNPs (MIC of 500 µg/ml) and were more resistant. Under static conditions, the sedimentation of SiNPs resulted in their ineffectiveness. However, under shaking conditions, the biofilms were effectively dispersed and the cells were lysed. The results showed that SiNPs were effective against both the planktonic and the metabolically inactive forms of P. aeruginosa. Conclusion: This study suggests that SiNPs could be a useful tool for preventing the formation of biofilms and removing pre-existing biofilms.

Rationale and Design of the Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT): A Pilot Study.

BACKGROUND: Cancer therapeutics-related cardiac dysfunction (CTRCD) is a well-recognised complication of cancer treatment. Treatment of CTRCD involves cardioprotective therapy (CPT) which can lead to a recovery of CTRCD with normalisation of the left ventricular ejection fraction (LVEF). As a result, there are potentially millions of cancer survivors with recovered CTRCD on CPT. Cardioprotective therapy can be associated with an undesirable long-term pill burden, financial costs, and side effects. Cancer survivorship is anticipated to increase significantly by the end of this decade. To date, there is no evidence of the safety of stopping CPT in this setting. This study seeks to evaluate the hypothesis that ceasing cardioprotective medication is a feasible and safe option without significant impact on LVEF in low-risk patients who have recovered from CTRCD. METHODS AND ANALYSIS: We will perform a multicentre prospective open-label randomised controlled trial with blinded endpoint (PROBE) of supervised CPT cessation compared to continuing CPT (control). The primary study end point is the change in LVEF by cardiac magnetic resonance imaging at 6 months of enrolment between the two groups. Secondary end points include changes in quality-of-life questionnaires, other cardiac imaging parameters, and recurrence of heart failure. CONCLUSION: Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT) is one of the first studies currently underway to evaluate the safety of ceasing CPT in recovered CTRCD. The results will inform clinical practice in this evidence-free zone.

Systematic Review of the Use of the 6-Minute Walk Test in Measuring and Improving Prognosis in Patients With Ischemic Heart Disease.

Introduction: The 6-minute walk test (6MWT) has been used for over 30 years to assess exercise capacity in patients with respiratory disease, and more recently, in those with heart failure. However, despite being a simple and reproducible test of real-world exercise capacity, its use in patients with ischemic heart disease (IHD) is less well accepted. We sought to review systematically the evidence surrounding the 6MWT in IHD. Methods: We searched the Medline, PubMed, Embase, and Scopus databases for the following key terms: "six minute walk test/6 minute walk test/6MWT" and "angina/coronary artery disease/coronary disease/IHD/ischemic heart disease." We followed Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines to select publications for full-text review and analyzed the collated data. Results: A total of 1228 unique papers were found, of which 71 were chosen for full-text review and 37 for detailed analysis. Most (23) concerned the effect on 6MWT distance (6MWTd) of cardiac rehabilitation, with measurements commenced after an intervention (acute myocardial infarction, n = 4; open heart surgery (OHS), n = 5; percutaneous coronary intervention (PCI), n = 3; or other, n = 11). The effect on 6MWTd of OHS was investigated in 6 studies and of PCI in one study. The 6MWT is a useful measurement of physical capacity; data are limited on its ability to assess benefit following PCI. Conclusions: The 6MWT has been studied inconsistently in IHD. The majority of data are on patients before and after CR. Data are limited concerning the effect on 6MWTd of OHS or PCI. The available data support the 6MWT as a measure of change in performance status following coronary intervention. More work is required to confirm this hypothesis.

Contexte: Le test de marche de 6 minutes (TM6) est utilisé depuis plus de 30 ans pour évaluer la tolérance à l'effort chez les patients atteints de maladies respiratoires, et maintenant également utilisé auprès des patients atteints d'insuffisance cardiaque. Toutefois, bien qu'il s'agisse d'un test simple et facile à reproduire de la tolérance à l'effort en contexte réel, son utilisation est moins bien acceptée auprès des patients présentant une cardiopathie ischémique (CI). Notre objectif était de réaliser une revue systématique des données probantes au sujet du TM6 chez les patients atteints de CI. Méthodologie: Nous avons effectué une recherche dans les bases de données Medline, PubMed, Embase et Scopus en utilisant les mots-clés suivants : « six minute walk test/6 minute walk test/6MWT ¼ [test de marche de six minutes/test de marche de 6 minutes/TM6] et « angina/coronary artery disease/coronary disease/IHD/ischemic heart disease ¼ [angine/coronaropathie/CI/cardiopathie ischémique]. Nous avons suivi les lignes directrices « Preferred Reporting Items for Systematic Reviews and Meta-analysis ¼ pour sélectionner les articles à soumettre à un examen du texte intégral et nous avons analysé les données obtenues. Résultats: Au total, 1 228 articles différents ont été repérés; 71 d'entre eux ont été sélectionnés pour un examen du texte intégral, puis 37 ont été soumis à une analyse plus détaillée. La plupart de ces articles (23) portaient sur l'effet de la distance au TM6 (dTM6) sur la réadaptation cardiaque, et les mesures débutaient après une intervention (infarctus aigu du myocarde, n = 4; chirurgie à cœur ouvert [CCO], n = 5; intervention coronarienne percutanée [ICP], n = 3; autre type d'intervention, n = 11). L'effet sur la dTM6 d'une CCO a été évalué dans six études et l'effet d'une ICP a été évalué dans une étude. La dTM6 est une mesure utile de la tolérance à l'effort, mais les données restent limitées sur sa capacité à évaluer les effets bénéfiques d'une ICP. Conclusions: L'utilisation du TM6 n'a pas été étudiée de façon systématique en contexte de CI. La majorité des données portent sur les patients avant et après la réadaptation cardiaque, mais il y a peu de données probantes sur l'effet d'une CCO ou d'une ICP sur la dTM6. Les données dont on dispose corroborent l'utilisation du TM6 comme mesure d'un changement des capacités après une intervention coronarienne. D'autres travaux de recherche devront être réalisés pour confirmer cette hypothèse.

Variations in indexation of left atrial volume across different races.

Background: Left atrial volume (LAV) has prognostic value. Guidelines propose indexation to body surface area (BSA), however studies demonstrate this can overcorrect for body size. Limited studies investigate indexation across different ethnicities. We sought to evaluate the effect of ethnicity on indexation. Methods: Using data from the World Alliance of Societies of Echocardiography (WASE) cohort, healthy subjects were classified by race as White, Black, Asian, or Other. Biplane LAV was indexed to traditional isometric measurements (BSA, height, weight, ideal body weight (IBW) and IBW derived BSA (IBSA)), as well as previously-derived allometric height exponents (2.7 and 1.72). Additionally, an allometric height exponent for our cohort was derived (linear regression of the logarithmic transformation of LAV = a(height)b) as 1.87. All indices were then assessed using Spearman correlation, with a good index retaining correlation of LAV/index to raw LAV (r∼1), while avoiding overcorrection by the index (r∼0). Results: There were 1366 subjects (White: 524, Black: 149, Asian: 523, Other: 170; median age 44 years, 653 females (47.8%)). In the entire group, BSA, IBSA, height1.87 and height1.72 performed well with retaining correlation to raw LAV (r > 0.9 for all), and minimising overcorrection to body size (r < 0.1 for all). On race-specific analysis, BSA overcorrected for body size in the White population (r = 0.128). Height1.72 minimised overcorrection for body size in all populations (r ≤ 0.1 for all races). Conclusion: Despite a cohort with normal BMI, there was still disparity in LAV indexation with BSA across races. Allometric height indexation, particularly using height1.72, is a possible solution, although further validation studies in BMI extremes are required.

Mitral regurgitation in the critically ill: the devil is in the detail.

Mitral regurgitation (MR) is common in the critically unwell and encompasses a heterogenous group of conditions with diverging therapeutic strategies. MR may present acutely with haemodynamic instability or more insidiously with failure to wean from mechanical ventilation. Critical illness is associated with marked physiological stress and haemodynamic changes that dynamically influence the severity and implication of MR. The expanding role of critical care echocardiography uniquely positions the intensivist to apply advanced bedside valvular assessment to recognise haemodynanically significant MR, manipulate and optimise cardiopulmonary physiology and identify patients requiring urgent cardiology and surgical referral. This review will consider common clinical scenarios, therapeutic strategies and the pearls and pitfalls of echocardiographic assessment and quantification in the critically unwell.

PDGF-AB Reduces Myofibroblast Differentiation Without Increasing Proliferation After Myocardial Infarction.

After myocardial infarction (MI), fibroblasts progress from proliferative to myofibroblast states, resulting in fibrosis. Platelet-derived growth factors (PDGFs) are reported to induce fibroblast proliferation, myofibroblast differentiation, and fibrosis. However, we have previously shown that PDGFs improve heart function post-MI without increasing fibrosis. We treated human cardiac fibroblasts with PDGF isoforms then performed RNA sequencing to show that PDGFs reduced cardiac fibroblasts myofibroblast differentiation and downregulated cell cycle pathways. Using mouse/pig MI models, we reveal that PDGF-AB infusion increases cell-cell interactions, reduces myofibroblast differentiation, does not affect proliferation, and accelerates scar formation. RNA sequencing of pig hearts after MI showed that PDGF-AB reduces inflammatory cytokines and alters both transcript variants and long noncoding RNA expression in cell cycle pathways. We propose that PDGF-AB could be used therapeutically to manipulate post-MI scar maturation with subsequent beneficial effects on cardiac function.

Health Economic Analysis of CMR: A Systematic Review.

INTRODUCTION: Uptake of cardiac magnetic resonance (CMR) in Australia has been limited by issues of cost and access. There is a need to inform future application of CMR by evaluating pertinent health economic literature. We sought to perform a systematic review on the health economic data as it pertains to CMR. METHODS: Eight databases (biomedical/health economic) were searched for relevant articles highlighting economic evaluations of CMR. Following screening, studies that reported health economic outcomes (e.g., dollars saved, quality adjusted life years [QALY] and cost effectiveness ratios) were included. Data on cost effectiveness, clinical/disease characteristics, type of modelling were extracted and summarised. RESULTS: Thirty-eight (38) articles informed the systematic review. Health economic models used to determine cost effectiveness included both trial-based studies (n=14) and Markov modelling (n=24). Comparative strategies ranged from nuclear imaging, stress echocardiography and invasive angiography. The disease states examined included coronary artery disease (23/38), acute coronary syndrome (3/38), heart failure (5/38) and miscellaneous (7/38). The majority of studies (n=29/38) demonstrated CMR as a strategy which is either economically dominant, cost-effective or cost-saving. CONCLUSION: This systematic review demonstrates that CMR is cost-effective depending on diagnostic strategy, population and disease state. The lack of standardised protocols for application of CMR, economic models used and outcomes reported limits the ability to meta-analyse the available health economic data.

Left ventricular longitudinal systolic dysfunction in children with type 1 diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVE: Children with type one diabetes mellitus (T1DM) may have subclinical myocardial insults but large heterogeneity exists among the reports. This study aimed to compare myocardial strain values of the left ventricle (LV) in paediatric patients with T1DM without overt cardiac disease and healthy controls. METHODS: Five databases (MEDLINE, Embase, Scopus, Web of Science and Cochrane central register of controlled trials) were searched from inception to March 30, 2020. The studies reporting two-dimensional speckle tracking echocardiography in asymptomatic T1DM paediatric patients and control groups were included. Pooled mean strain values in each group and mean difference (MD) between the two groups for LV global longitudinal strain (LVGLS) and LV global circumferential strain (LVGCS) were assessed using a random effects model. RESULTS: Ten studies (755 T1DM and 610 control) with LVGLS were included with 6 studies having LVGCS (534 T1DM and 403 control). Patients with T1DM had overall 3 percentage points lower LVGLS than healthy subjects (18.4 %, 95 % confidence interval [17.1, 19.6] vs 21.5 % [20.3, 22.7], MD = -3.01 [-4.30, -1.71]). A similar result was seen in LVGCS (18.7 % [15.4, 22.0] vs. 21.4 % [18.1, 24.6], MD = -3.10[-6.47, 0.26]) but not statistically significant. Meta-regression identified those with higher Haemoglobin A1c (HbA1c) had worse GLS. CONCLUSIONS: Subclinical LV dysfunction among patients with T1DM occurs as early as in their childhood, while even EF is preserved. The longitudinal cardiac function is altered, but not the circumferential. GLS can be used to detect subclinical LV systolic dysfunction in paediatric population.

Cardiac magnetic relaxometry versus ejection fraction in anthracycline-related cardiac changes: a systematic review and meta-analysis.

PURPOSE: The purpose of this meta-analysis is to compare the magnitude of the changes in left ventricular ejection fraction (LVEF) and cardiac magnetic resonance (CMR) relaxometry techniques soon after the completion of anthracycline therapy. Anthracyclines are associated with myocardial functional and morphological changes. LVEF is currently used to identify the functional changes. Anthracyclines can also cause myocardial inflammation and oedema. This can be assessed using CMR relaxometry techniques; T1 and T2 mapping and extracellular volume (ECV) fraction. METHODS: Three databases were systematically searched for studies evaluating CMR relaxometry parameter at baseline and 1±1 months after anthracycline completion (the last search date 17 March 2023). CMR parameters pre and post anthracycline-based chemotherapy were abstracted. A random effects model was used to pool mean difference (MD) in LVEF and ECV. Standardised mean difference (SMD) was also calculated for T1 and T2 mapping due to the variations in techniques, normal ranges and for the comparison among the parameters. RESULTS: A total of 296 patients were included from 10 studies. 84% were female with a mean age of 54.9 years. Statistically significant alterations were observed in LVEF (MD -3.38% (95% CI -5.13%, -1.62%)) and ECV (1.92% (1.30%, 2.53%)). The pooled SMDs were also significant in LVEF, T1, T2 and ECV with -0.61 (-0.91, -0.30), 0.53 (0.16, 0.90), 0.59 (0.22, 0.96) and 0.74 (0.41, 1.06), respectively. CONCLUSIONS: Our meta-analysis demonstrated small but significant alterations in CMR relaxometry parameters soon after anthracycline therapy, where ECV was superior to LVEF and T1 or T2 mapping. However, these short-term MDs were below the minimal detectable differences. PROSPERO REGISTRATION NUMBER: CRD42020196296.

Artificial Intelligence in Cardiology: An Australian Perspective.

Significant advances have been made in artificial intelligence technology in recent years. Many health care applications have been investigated to assist clinicians and the technology is close to being integrated into routine clinical practice. The high prevalence of cardiac disease in Australia places overwhelming demands on the existing health care system, challenging its capacity to provide quality patient care. Artificial intelligence has emerged as a promising solution. This discussion paper provides an Australian perspective on the current state of artificial intelligence in cardiology, including the benefits and challenges of implementation. This paper highlights some current artificial intelligence applications in cardiology, while also detailing challenges such as data privacy, ethical considerations, and integration within existing health infrastructures. Overall, this paper aims to provide insights into the potential benefits of artificial intelligence in cardiology, while also acknowledging the barriers that need to be addressed to ensure safe and effective implementation into an Australian health system.

Subclinical systolic dysfunction detected by 2D speckle tracking echocardiography in adults with diabetes mellitus: systematic review and meta-analysis of 6668 individuals with diabetes mellitus and 7218 controls.

PURPOSE: Speckle tracking echocardiography (STE) can help to identify subclinical features of diabetic cardiomyopathy (DCM). There is, however, significant heterogeneity in the reported strain values in literature. We performed a systematic review and meta-analysis to compare cardiac systolic strain values assessed by 2D-STE in asymptomatic adults with diabetes mellitus (DM) and healthy controls. METHODS: Five databases were searched, and a total of 41 valid studies (6668 individuals with DM and 7218 controls) were included for analysis. Pooled mean in each group and mean difference (MD) for left ventricular global longitudinal strain (LVGLS), LV global circumferential strain (LVGCS), LV global radial strain (LVGRS), LV longitudinal systolic strain rate (LVSR), left atrial reservoir strain (LARS) and right ventricular GLS (RVGLS) were assessed. RESULTS: Patients with DM had overall 2 units lower LVGLS than healthy subjects 17.5% [16.8, 18.3], vs 19.5 [18.7, 20.4], MD = - 1.96 [- 2.27, - 1.64]. Other strain values were also lower in patients with DM: LVGCS (MD = - 0.89 [- 1.26, - 0.51]); LVGRS (MD = - 5.03 [- 7.18, - 2.87]); LVSR (MD = - 0.06 [- 0.10, - 0.03]); LARS (MD = - 8.41 [- 11.5, - 5.33]); and RVGLS (MD = - 2.41 [- 3.60, - 1.22]). Meta-regression identified higher body mass index (BMI) as the single contributor to worse LVGLS, LVGCS and LVSR. Those with higher Hemoglobulin A1c had worse RVGLS. CONCLUSION: Myocardial strains were reduced in whole heart in patients with DM. The largest reduction was observed in LA reservoir strain, followed by RVGLS and LVGLS. Higher BMI in patients with DM is associated with worse LV strain values.

Kidney Adverse Events Associated with Immune Checkpoint Inhibitor Therapy: A Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: The blockade of immune regulatory sites, CTLA-4, PD-1, and PD-L1 with Immune Checkpoint Inhibitors has revolutionized survival outcomes in cancer patients. However, immune checkpoint inhibitors are associated with a range of immune related adverse events. The aim of this network meta-analysis is to evaluate severe adverse kidney events in patients with oncological or hematological malignancy receiving monotherapy, dual therapy or combined therapy treatment with immune checkpoint inhibitors when compared to either placebo or standard chemotherapy. METHODS: Phase III Randomized Control Trials reporting severe grade (3-5) adverse kidney events were identified across five electronic databases from inception to May 2022. This was supplemented with hand searching of medical journals and the National Clinical Trials registry. A Bayesian network meta-analysis was performed for: acute kidney injury, hypertension, chronic kidney disease and the composite of all acute kidney adverse events. The results are reported as per PRISMA guidelines. RESULTS: 95 randomized control trials reported severe grade adverse kidney events. The risk of developing severe acute kidney injury is higher among patients who received PD-1 plus chemotherapy (OR 1.8 [95% CrI 1.4 to 2.5]) and PD-L1 plus chemotherapy (OR 1.80 [95% CrI 1.2 to 2.7]) compared to standard chemotherapy and placebo (94 studies, 63, 357 participants). The risk of developing the composite of all severe acute kidney adverse events is higher among patients who received PD-1 plus chemotherapy (OR 1.6 [95% CrI 1.1 to 2.3]) and PD-L1 plus chemotherapy (OR 1.7 [95% CrI 1.1 to 2.8) when compared to standard chemotherapy and placebo (95 studies, 63, 973 participants). CONCLUSIONS: The combined regimen of PD-1 + chemotherapy and PD-L1 + chemotherapy was associated with higher incidence of severe acute kidney injury and the composite of all severe acute kidney adverse events.