Variability in approach to exercise stress echocardiography for diagnosis of heart failure with preserved ejection fraction: an international survey on real-world practice.

Aims: The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging based on resting assessments. Exercise echocardiography is often used to unmask abnormalities that develop during exercise, but the diagnostic criteria have not been standardized. This study aimed to elucidate how cardiologists utilize exercise echocardiography to diagnose HFpEF in real-world practice. Methods and results: An international web-based survey involving 87 cardiologists was performed. We also performed a retrospective cross-sectional study to investigate the impact of different exercise echocardiographic diagnostic criteria in 652 dyspnoeic patients who underwent exercise echocardiography. The HFA-PEFF algorithm was the most commonly used exercise echocardiography criterion for HFpEF diagnoses (48%), followed by the ASE/EACVI criteria (24%) and other combinations of multiple parameters (22%). Among 652 patients, the proportion of HFpEF diagnosis varied substantially according to the criteria used ranging from 20.1% (ASE/EACVI criteria) to 44.3% (HFA-PEFF algorithm). Many cases (49.4-70.5%) remained indeterminate after exercise echocardiography, but only 41% of surveyed cardiologists would utilize exercise right heart catheterization to resolve an indeterminate result. Despite these diagnostic uncertainties, 54% of surveyed cardiologists would utilize exercise echocardiography results to initiate sodium-glucose co-transporter 2 inhibitors. Conclusion: In real-world practice, exercise echocardiographic criteria utilized across cardiologists vary, which meaningfully impacts the frequency of HFpEF diagnoses, with indeterminate results being common. Despite these diagnostic uncertainties, many cardiologists initiate pharmacotherapy based on exercise echocardiography. The lack of consensus on universal diagnostic criteria for exercise echocardiography and approaches to indeterminate results may limit the delivery of evidence-based treatment for HFpEF.

Strain surveillance during chemotherapy to improve cardiovascular outcomes: the SUCCOUR-MRI trial.

BACKGROUND AND AIMS: The detection of cancer therapy-related cardiac dysfunction (CTRCD) by reduction of left ventricular ejection fraction (LVEF) during chemotherapy usually triggers the initiation of cardioprotective therapy. This study addressed whether the same approach should be applied to patients with worsening of global longitudinal strain (GLS) without attaining thresholds of LVEF. METHODS: Strain sUrveillance during Chemotherapy for improving Cardiovascular Outcomes (SUCCOUR-MRI) was a prospective multicentre randomized controlled trial involving 14 sites. Of 355 patients receiving anthracyclines with normal baseline LVEF, 333 patients (age 59±13 years, 79% women) with at least one other CTRCD risk factor, able to undergo magnetic resonance imaging (MRI), GLS and 3D echocardiography were tracked over 12 months. A total of 105 patients (age 59±13 years, 75% women, 69% breast cancer) developing GLS-CTRCD (>12% relative reduction of GLS without a change in LVEF) between cardioprotection with neurohormonal antagonists versus usual care were randomized. The primary endpoint was 12-month change in MRI-LVEF; the secondary endpoint was MRI LVEF-defined CTRCD. RESULTS: During follow-up, 2 patients died and 2 developed heart failure. Most patients were randomized at 3 months (62%). Median doses of angiotensin inhibition/blockade and beta-blockade were 75% and 50% of respective targets; 21 (43%) had side-effects attributed to cardioprotection. Due to a smaller LVEF change from baseline with cardioprotection than usual care (-2.5±5.4% vs -5.6±5.9%, p=0.009), follow-up LVEF was higher after cardioprotection (59±5% vs 55±6%, p<0.0001). After adjustment for baseline LVEF, the mean (95% confidence interval) difference in the change in LVEF between the two groups was -3.6% (-1.8% to -5.5%, p<0.001). After cardioprotection, 1/49 patients developed 12-month LVEF-CTRCD, compared to 6/56 in usual care (p=0.075). GLS improved at 3 months post-randomization in the cardioprotection group, with little change with usual care. CONCLUSIONS: In patients with isolated GLS reduction after anthracyclines, cardioprotection is associated with better preservation of 12-month MRI-LVEF compared with usual care.

Sonothrombolysis Before and After Percutaneous Coronary Intervention Provides the Largest Myocardial Salvage in ST Segment Elevation Myocardial Infarction.

BACKGROUND: Sonothrombolysis is a therapeutic application of ultrasound with ultrasound contrast for patients with ST elevation myocardial infarction (STEMI). Recent trials demonstrated that sonothrombolysis, delivered before and after primary percutaneous coronary intervention (pPCI), increases infarct vessel patency, improves microvascular flow, reduces infarct size, and improves ejection fraction. However, it is unclear whether pre-pPCI sonothrombolysis is essential for therapeutic benefit. We designed a parallel 3-arm sham-controlled randomized controlled trial to address this. METHODS: Patients presenting with first STEMI undergoing pPCI within 6 hours of symptom onset were randomized 1:1:1 into 3 arms: sonothrombolysis pre-/post-pPCI (group 1), sham pre- sonothrombolysis post-pPCI (group 2), and sham pre-/post-pPCI (group 3). Our primary end point was infarct size (percentage of left ventricular mass) assessed by cardiac magnetic resonance imaging at day 4 ± 2. Secondary end points included myocardial salvage index (MSI) and echocardiographic parameters at day 4 ± 2 and 6 months. RESULTS: Our trial was ceased early due to the COVID pandemic. From 122 patients screened between September 2020 and June 2021, 51 patients (age 60, male 82%) were included postrandomization. Median sonothrombolysis took 5 minutes pre-pPCI and 15 minutes post-, without significant door-to-balloon delay. There was a trend toward reduction in median infarct size between group 1 (8% [interquartile range, 4,11]), group 2 (11% [7, 19]), or group 3 (15% [9, 22]). Similarly there was a trend toward improved MSI in group 1 (79% [64, 85]) compared to groups 2 (51% [45, 70]) and 3 (48% [37, 73]) No major adverse cardiac events occurred during hospitalization. CONCLUSIONS: Pre-pPCI sonothrombolysis may be key to improving MSI in STEMI. Multicenter trials and health economic analyses are required before clinical translation.

Impact of maternal diabetes mellitus on fetal atrial strain.

While Maternal Diabetes Mellitus (DM) is well known to affect the size and function of multiple fetal organ systems, effects on developing heart chamber function remain difficult to assess. We sought to determine the independent impact of maternal DM on fetal cardiac function in middle pregnancy. We prospectively recruited mothers with all categories of DM and non-diabetic healthy controls (NDC). Echocardiograms were optimized for chamber quantification and strain analysis. Left atrial area (LAA), LA strain (LAS), right atrial strain (RAS), global longitudinal ventricular strain (GLS) and Right ventricular free wall strain (RV FWS) were evaluated by 2 blinded operators. After excluding 9 mothers with poor fetal image quality, images from 104 mothers with DM and 47 NDC were analyzed. Mothers with DM and NDCs were well matched for age, blood pressure, smoking prevalence, and gestational age. Fetal heart rate (FHR) was significantly higher in fetuses of mothers with DM compared to NDC (147 ± 10 bpm vs. 144 ± 8, p = 0.04). LAA in fetuses of mothers with DM trended towards being larger in size (1.68 ± 0.4cm2 vs. 1.56 ± 0.4cm2, p = 0.08). Fetal septal diameters were larger in maternal DM compared to NDC (2.7 ± 0.5 cm vs. 2.5 ± 0.5 cm, p = 0.001). GLS was similar between the groups. Fetal LAS was lower in maternal DM (28.8 ± 8.8% vs. 33.3 ± 10.4%, p = 0.007) and was independently associated with maternal DM after adjusting for GLS and FHR. Fetal RAS was lower in maternal DM (27.7 ± 10.4% vs. 31.8 ± 10.3%, p = 0.007), however only determinates were estimated fetal weight and RV FWS. Maternal DM independently impairs fetal LA function in mid pregnancy. These early functional changes in the developing heart warrant future studies investigating impact on cardiovascular health.

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 2 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 6 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.

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.

Increased vascular stiffness in children exposed in utero but not children exposed postnatally to emissions from a coal mine fire.

Background: Chronic, low-intensity air pollution exposure has been consistently associated with increased atherosclerosis in adults. However, there was limited research regarding the implications of acute, high-intensity air pollution exposure during childhood. We aimed to determine whether there were any associations between early-life exposure to such an episode and early-life vascular function changes. Methods: We conducted a prospective cohort study of children (<9 years old) who lived in the vicinity of the Hazelwood coal mine fire (n = 206). Vascular function was measured using noninvasive diagnostic methods including carotid intima-media thickness and pulse wave velocity (PWV). Exposure estimates were calculated from prognostic models and location diaries during the exposure period completed by each participant's parent. Linear mixed-effects models were used to determine whether there were any associations between exposure and changes in vascular outcomes at the 3- and 7-year follow-ups and over time. Results: At the 7-year follow-up, each 10 µg/m3 increase in daily PM2.5 in utero was associated with increased PWV (ß = 0.13 m/s; 95% confidence interval [CI] = 0.02, 0.24; P = 0.02). The association between in utero exposure to daily PM2.5 was not altered by adjustment for covariates, body mass index, and maternal fire stress. Each 1 µg/m3 increase in background PM2.5 was associated with increased PWV (ß = 0.68 m/s; 95% CI = 0.10, 1.26; P = 0.025), in children from the in utero exposure group. There was a trend toward smaller PWV (ß = -0.17 m/s; 95% CI = -0.366, 0.02) from the 3- to 7-year follow-up clinic suggesting that the deficits observed previously in children exposed postnatally did not persist. Conclusion: There was a moderate improvement in vascular stiffness of children exposed to PM2.5 from a local coal mine fire in infancy. There was a mild increase in vascular stiffness in children exposed to PM2.5 from a local coal mine fire while their mothers were pregnant.

Tracking of serum lipid levels from childhood to adulthood: Systematic review and meta-analysis.

BACKGROUND AND AIMS: The utility of lipid screening in pediatric settings for preventing adult atherosclerotic cardiovascular diseases partly depends on the lifelong tracking of lipid levels. This systematic review aimed to quantify the tracking of lipid levels from childhood and adolescence to adulthood. METHODS: We systematically searched MEDLINE, Embase, Web of Science, and Google Scholar in March 2022. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; ID: CRD42020208859). We included cohort studies that measured tracking of lipids from childhood or adolescence (<18 years) to adulthood (≥18) with correlation or tracking coefficients. We estimated pooled correlation and tracking coefficients using random-effects meta-analysis. Risk of bias was assessed with a review-specific tool. RESULTS: Thirty-three studies of 19 cohorts (11,020 participants) were included. The degree of tracking from childhood and adolescence to adulthood differed among lipids. Tracking was observed for low-density lipoprotein cholesterol (pooled r = 0.55-0.65), total cholesterol (pooled r = 0.51-0.65), high-density lipoprotein cholesterol (pooled r = 0.46-0.57), and triglycerides (pooled r = 0.32-0.40). Only one study included tracking of non-high-density lipoprotein cholesterol (r = 0.42-0.59). Substantial heterogeneity was observed. Study risk of bias was moderate, mostly due to insufficient reporting and singular measurements at baseline and follow-up. CONCLUSIONS: Early-life lipid measurements are important for predicting adult levels. However, further research is needed to understand the tracking of non-high-density lipoprotein cholesterol and the stability of risk classification over time, which may further inform pediatric lipid screening and assessment strategies.

Blood Pressure Lowering in Patients With Central Hypertension: A Randomized Clinical Trial.

BACKGROUND: Cuff blood pressure (BP) is recommended for guiding hypertension management. However, central BP has been proposed as a superior clinical measurement. This study aimed to determine whether controlling hypertension as measured by central BP was beneficial in reducing left ventricular mass index beyond control of standard cuff hypertension. METHODS: This multicenter, open-label, blinded-end point trial was conducted in individuals treated for uncomplicated hypertension with controlled cuff BP (<140/90 mm Hg) but elevated central BP (≥0.5 SD above age- and sex-specific normal values). Participants were randomized to 24-months intervention with spironolactone 25 mg/day (n=148) or usual care control (n=153). The primary outcome was change in left ventricular mass index measured by cardiac MRI. Cuff and central BPs were measured by clinic, 7-day home and 24-hour ambulatory BPs. RESULTS: At 24-months, there was a greater reduction in left ventricular mass index (-3.2 [95% CI, -5.0 to -1.3] g/m2; P=0.001) with intervention compared with control. Cuff and central BPs were lowered by a similar magnitude across all BP measurement modes (eg, clinic cuff systolic BP, -6.16 [-9.60 to -2.72] mm Hg and clinic central systolic BP, -4.96 [-8.06 to -1.86] mm Hg; P≥0.48 all). Secondary analyses found that changes in left ventricular mass index correlated to changes in BP, with the magnitude of effect nearly identical for BP measured by cuff (eg, 24-hour systolic BP, ß, 0.17 [0.02-0.31] g/m2) or centrally (24-hour systolic BP, ß, 0.16 [0.01-0.32] g/m2). CONCLUSIONS: Among individuals with central hypertension, spironolactone had beneficial effects in reducing LV mass. Secondary analyses showed that changes in LV mass were equally well associated with lower measured standard cuff BP and central BP. REGISTRATION: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12613000053729.

Integrating Cardio-Oncology Across the Research Pipeline, Policy, and Practice in Australia-An Australian Cardiovascular Alliance Perspective.

Over 18 million people worldwide were diagnosed with cancer in 2020, including over 150,000 people in Australia. Although improved early detection and treatment have increased the survival rates, cardiotoxic treatment and inadequate management of cardiovascular risk factors have resulted in cardiovascular disease (CVD) being one of the leading causes of non-cancer-related death and disability among cancer survivors. International guidelines outline the standards of care for CVD risk surveillance and management. However, Australian cardio-oncology policies and clinical guidelines are limited. There is increasing growth of cardio-oncology research in Australia and support from leading Australian professional bodies and advocacy and research networks, including the Cardiac Society of Australia and New Zealand, the Clinical Oncology Society of Australia, the National Heart Foundation of Australia, and the Australian Cardiovascular Alliance (ACvA). Thus, opportunities to drive multidisciplinary cardio-oncology initiatives are growing, including grant funding, position statements, and novel research to inform new policies. The ACvA has a unique flagship structure that spans the translational research pipeline from drug discovery to implementation science. This article aims to highlight how multidisciplinary cardio-oncology innovations could intersect with the seven ACvA flagships, and to showcase Australian achievements in cardio-oncology thus far. We summarise eight key priority areas for future cardio-oncology research that emerged. These strategies will strengthen cardio-oncology research and care in Australia, and drive new guidelines, policies, and government initiatives to ensure equity in health outcomes for all cardio-oncology patients.

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.

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.

Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors: JACC State-of-the-Art Review.

Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed.

The impact of body mass index on cardiac structure and function in a cohort of obese patients without traditional cardiovascular risk factors.

Background: Obesity has been linked with alterations in hemodynamic, autonomic, and hormonal pathways in the body, leading to a spectrum of cardiovascular changes. We sought to evaluate the effects of obesity on structural and functional changes of the heart in the absence of cardiac disease and associated risk factors. Methods: We identified healthy outpatients without any cardiovascular disease or risk factors from our institution's echocardiography database (2017-2020). Patients were stratified by body mass index (BMI; normal: 18.5-25 kg/m2; overweight: 25-30 kg/m2; class 1 obesity: 30-35 kg/m2; class 2 obesity: 35-40 kg/m2; class 3 obesity: >40 kg/m2). Traditional and advanced echocardiographic parameters of cardiac chamber size and function including left ventricular global longitudinal strain (LV-GLS), left atrial reservoir strain (LASr), and right ventricular free wall strain (RV-FWS) were examined. The optimal cut-off BMI for discriminating LV-GLS (>-17.5%), LASr (<23%), and RV-FWS (>-23%) impairment was calculated using ROC curves. Results: 307 patients were assessed (41.5 ± 13.3yrs; 36.5%male; LVEF 61.3 ± 4.8%). No significant differences in indexed chamber volumes or LVEF were appreciated across BMI groups (p > 0.05 for all). LV-GLS, LASr, and RV-FWS were all significant on one-way ANOVA for differences from the group mean (all p < 0.01). Jonckheere-Terpstra test confirmed a significant trend of lower absolute LV-GLS, LASr and RV-FWS values across the rising BMI groups. On ROC curve analysis, a BMI value of 29.9 kg/m2, 35.1 kg/m2, and 37.3 kg/m2 were associated with LASr (AUC: 0.75), RV-FWS (AUC: 0.72), and LV-GLS (AUC: 0.75) impairment respectively. Conclusion: Obesity is linked with subclinical reduction of cardiac function in otherwise healthy subjects without cardiovascular risk factors, with reduction of left atrial function occurring at lower BMI, followed by the right and left ventricular function.

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.

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.