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.

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.

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.

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.

Cardiac Autonomic Impacts of Bushfire Smoke-A Prospective Panel Study.

BACKGROUND: Air pollution is associated with cardiovascular disease and mortality. Most studies have focussed on urban or traffic-related pollution, and less is known about the impacts from bushfire smoke on cardiovascular autonomic function, although it is associated with increased sudden cardiac death and mortality. We sought to investigate its instantaneous and short-term impacts on heart rate variability (HRV). METHODS: Twenty-four (24)-hour Holter electrocardiography (ECG) was repeated twice (during bushfire [Phase 1] and then clean air [Phase 2]) in 32 participants from two Australian towns (Warburton and Traralgon, Victoria) surrounding planned burning areas. This was compared with 10 control participants in another town (Maffra, Victoria) with two clean air assessments during the same periods. The primary HRV parameters assessed were those assessing overall HRV (Standard Deviation of Normal-to-Normal intervals [SDNN]), long-term HRV (Standard Deviation of the Average of Normal Sinus-to-Normal Sinus intervals for each 5-minutes [SDANN]), low frequency [LF]) and short-term HRV (Root Mean Square of Successive Differences between N-N intervals [RMSSD], High Frequency [HF], LF:HF ratio). Average concentrations of particulate matter <2.5 µm in diameter (PM2.5) were measured at fixed site monitors in each location. RESULTS: Mean PM2.5 levels were significantly elevated during bushfire exposure in Warburton (96.5±57.7 µg/m3 vs 4.0±1.9 µg/m3, p<0.001) and Traralgon (12.6±4.9 µg/m3 vs 3.4±3.1 µg/m3, p<0.001), while it remained low in the control town, Maffra, in each phase (4.3±3.2 µg/m3 and 3.9±3.6 µg/m3, p=0.70). Although SDANN remained stable in controls, the exposed cohort showed significant worsening in SDANN during bushfire smoke exposure by 9.6±25.7ms (p=0.039). In univariable analysis, smoke exposure was significantly associated with higher ΔSDNN and ΔSDANN (p=0.03, p=0.01 exposed vs control). The association remained significant in ΔSDANN after adjusting for age, sex and cigarette smoking (p=0.02) and of borderline significance in ΔSDNN (p=0.06). CONCLUSIONS: Exposure to the bushfire smoke was independently associated with reduced overall and long-term HRV. Our findings suggest that imbalance in cardiac autonomic function is a key mechanism of adverse cardiovascular effects of bushfire smoke.

Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3-Year Results of the SUCCOUR Trial.

BACKGROUND: Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction and guide initiation of cardioprotection (CPT). OBJECTIVES: In this study, the authors sought to determine whether echocardiography GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care at 3 years. METHODS: In this international multicenter prospective randomized controlled trial, patients were enrolled from 28 international sites. All patients treated with anthracyclines with another risk factor for heart failure were randomly allocated to GLS-guided (>12% relative reduction in GLS) or ejection fraction (EF)-guided (>10% absolute reduction of EF to <55%) CPT. The primary end point was the change in 3-dimensional (3D) EF (ΔEF) from baseline to 3 years. RESULTS: Among 331 patients enrolled, 255 (77%, age 54 ± 12 years, 95% women) completed 3-year follow-up (123 in the EF-guided group and 132 in the GLS-guided group). Most had breast cancer (n = 236; 93%), and anthracycline followed by trastuzumab was the most common chemotherapy regimen (84%). Although 67 (26%) had hypertension and 32 (13%) had diabetes mellitus, left ventricular function was normal at baseline (EF: 59% ± 6%, GLS: 20.7% ± 2.3%). CPT was administered in 18 patients (14.6%) in the EF-guided group and 41 (31%) in the GLS-guided group (P = 0.03). Most patients showed recovery in EF and GLS after chemotherapy; 3-year ΔEF was -0.03% ± 7.9% in the EF-guided group and -0.02% ± 6.5% in the GLS-guided (P = 0.99) group; respective 3-year EFs were 58% ± 6% and 59% ± 5% (P = 0.06). At 3 years, 17 patients (5%) had cancer therapeutics-related cardiac dysfunction (11 in the EF-guided group and 6 in the GLS guided group; P = 0.16); 1 patient in each group was admitted for heart failure. CONCLUSIONS: Among patients taking potentially cardiotoxic chemotherapy for cancer, the 3-year data showed improvement of LV dysfunction compared with 1 year, with no difference in ΔEF between GLS- and EF-guided CPT. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).

Role of Myocardial Strain Imaging in Cancer Therapy-Related Cardiac Dysfunction.

PURPOSE OF REVIEW: This review aims to provide a contemporary perspective on the role of myocardial strain imaging in the management of patients on cardiotoxic therapy. RECENT FINDINGS: Risk/benefit evaluation of cardiotoxic cancer treatment remains challenging, weighing life-saving cancer therapy with fatal cardiac dysfunction potentially caused by cancer therapy. The serial change in left ventricular ejection fraction (LVEF) was conventionally used for the detection of cancer therapy-related cardiac dysfunction (CTRCD). Peak systolic global longitudinal strain (GLS) by speckle-tracking echocardiography has turned into a vital pre- and post-chemotherapy assessment for the early detection of cardiotoxicity. Complexity in cardiotoxic therapy regimen, different definition of CTRCD by LVEF, variations in GLS values, timings, and variable cutoffs make it challenging to standardize the protocol for the detection of CTRCD. GLS > 15% relative reduction from baseline has been widely used. Evidence suggests that GLS could predict early subclinical LV dysfunction, and initiation of cardioprotective therapy led to less decline of LV function. Most of the studies used an echocardiographic endpoint, and the impact of GLS on the long-term clinical outcome is not established. GLS has emerged as a reliable measure to identify early subclinical LV dysfunction by detecting myocardial deformation in patients on cardiotoxic chemotherapy. To date, a significant decline in GLS suggests the initiation of cardioprotective therapy with close monitoring. Interruption of prognostically important cardiotoxic chemotherapies requires a multidisciplinary team approach guided mainly by LVEF and other clinical factors. Further randomized control trials with hard clinical endpoints and longer follow-ups may help to determine the role of GLS in CTRCD.

Incremental Value of Myocardial Work over Global Longitudinal Strain in the Surveillance for Cancer-Treatment-Related Cardiac Dysfunction: A Case-Control Study.

The load dependence of global longitudinal strain (GLS) means that changes in systolic blood pressure (BP) between visits may confound the diagnosis of cancer-treatment-related cardiac dysfunction (CTRCD). We sought to determine whether the estimation of myocardial work, which incorporates SBP, could overcome this limitation. In this case-control study, 44 asymptomatic patients at risk of CTRCD underwent echocardiography at baseline and after oncologic treatment. CTRCD was defined on the basis of the change in the ejection fraction. Those with CTRCD were divided into subsets with and without a follow-up SBP increment >20 mmHg (CTRCD+BP+ and CTRCD+BP-), and matched with patients without CTRCD (CTRCD-BP+ and CTRCD-BP-). The work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were assessed in addition to the GLS. The largest increases in the GWI and GCW at follow-up were found in CTRCD-BP+ patients. The CTRCD+BP- patients demonstrated significantly larger decreases in GWI and GCW than their CTRCD+BP+ and CTRCD-BP- peers. ROC analysis for the discrimination of LV functional changes in response to increased afterload in the absence of cardiotoxicity revealed higher AUCs for GCW (AUC = 0.97) and GWI (AUC = 0.93) than GLS (AUC = 0.73), GWW (AUC = 0.51), or GWE (AUC = 0.63, all p-values < 0.001). GCW (OR: 1.021; 95% CI: 1.001-1.042; p < 0.04) was the only feature independently associated with CTRCD-BP+. Myocardial work is superior to GLS in the serial assessments in patients receiving cardiotoxic chemotherapy. The impairment of GLS in the presence of an increase in GWI and GCW indicates the impact of elevated afterload on LV performance in the absence of actual myocardial impairment.

The Utility of Advanced Cardiovascular Imaging in Cancer Patients-When, Why, How, and the Latest Developments.

Cardio-oncology encompasses the risk stratification, prognostication, identification and management of cancer therapeutics related cardiac dysfunction (CTRCD). Cardiovascular imaging (CVI) plays a significant role in each of these scenarios and has broadened from predominantly quantifying left ventricular function (specifically ejection fraction) to the identification of earlier bio-signatures of CTRCD. Recent data also demonstrate the impact of chemotherapy on the right ventricle, left atrium and pericardium and highlight a possible role for CVI in the identification of CTRCD through tissue characterization and assessment of these cardiac chambers. This review aims to provide a contemporary perspective on the role of multi-modal advanced cardiac imaging in cardio-oncology.

Associations between respiratory and vascular function in early childhood.

BACKGROUND AND OBJECTIVE: The link between respiratory and vascular health is well documented in adult populations. Impaired lung function is consistently associated with thicker arteries and higher incidence of cardiovascular disease. However, there are limited data on this relationship in young children and the studies that exist have focussed on populations at high risk of cardiorespiratory morbidity. We determined if an association exists between respiratory and cardiovascular function in young children and, if so, whether it is confounded by known cardiorespiratory risk factors. METHODS: Respiratory and vascular data from a prospective cohort study established to evaluate the health implications 3 years after coal mine fire smoke exposure in children aged 3-5 years were used. Respiratory function was measured using the forced oscillation technique and included resistance at 5 Hz (R5 ), reactance at 5 Hz (X5 ) and area under the reactance curve (AX). Vascular health was measured by carotid intima-media thickness (ultrasound) and pulse wave velocity (arterial tonometry). Regression analyses were used to examine the relationship between the respiratory Z-scores and cardiovascular measures. Subsequent analyses were adjusted for potential confounding by maternal smoking during pregnancy, maternal education and exposure to fine particulate matter <2.5 µm in aerodynamic diameter (PM2.5 ). RESULTS: Peripheral lung function (X5 and AX), but not respiratory system resistance (R5 ), was associated with vascular function. Adjustment for maternal smoking, maternal education and early life exposure to PM2.5 had minimal effect on these associations. CONCLUSION: These observations suggest that peripheral lung stiffness is associated with vascular stiffness and that this relationship is established early in life.

Cardiotoxic Effect of Modern Anthracycline Dosing on Left Ventricular Ejection Fraction: A Systematic Review and Meta-Analysis of Placebo Arms From Randomized Controlled Trials.

Background Anthracyclines are a key chemotherapeutic agent used against hematological and solid organ malignancies. However, their benefits in cancer survival are limited by cumulative, dose-related cardiotoxicity. The impact of anthracyclines on left ventricular ejection fraction (LVEF), in the era of modern chemotherapy regimens, remains unclear. Methods and Results Three databases (CENTRAL, MEDLINE, and SCOPUS) were systematically searched for randomized trials evaluating cardioprotective agents against placebo, in preventing cardiotoxicity. Echocardiography or magnetic resonance measured LVEF pre- and post-anthracycline-based chemotherapy was abstracted from placebo trial arms. The key terms included "anthracycline," "cardiotoxicity" and "randomized." A doxorubicin equivalent anthracycline dose metric was calculated to compare different anthracyclines. A random-effects model was used to pool mean difference in LVEF after anthracycline. Meta-regressions were calculated to identify variation sources. We included 660 patients from 19 trials. The weighted mean baseline LVEF across studies was 62.6%, and follow-up LVEF assessment was performed at 6 months. The pooled mean decline in LVEF among placebo arms was 5.4% (95% CI, 3.5%-7.3%) with a doxorubicin equivalent anthracycline dose of 385 mg/m2. Meta-regression analysis showed no significant difference in LVEF against doxorubicin equivalent anthracycline dose as continuous (P=0.29) or against published cut-offs for cardiotoxicity (250 mg/m2, P=0.21; 360 mg/m2, P=0.40; and 400 mg/m2, P=0.66). The differences in mean LVEF were not associated with sex, adjunct chemotherapy, or cancer type. Conclusions The magnitude of LVEF impairment post-anthracycline therapy appears less than previously described with modern dosing regimens. This may improve the accuracy of power calculation for future clinical trials assessing the role of cardioprotective therapy.

Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy.

BACKGROUND: In patients at risk of cancer therapy-related cardiac dysfunction (CTRCD), initiation of cardioprotective therapy (CPT) is constrained by the low sensitivity of ejection fraction (EF) for minor changes in left ventricular (LV) function. Global longitudinal strain (GLS) is a robust and sensitive marker of LV dysfunction, but existing observational data have been insufficient to support a routine GLS-guided strategy for CPT. OBJECTIVES: This study sought to identify whether GLS-guided CPT prevents reduction in LVEF and development of CTRCD in high-risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care. METHODS: In this international, multicenter, prospective, randomized controlled trial, 331 anthracycline-treated patients with another heart failure risk factor were randomly allocated to CPT initiation guided by either ≥12% relative reduction in GLS (n = 166) or >10% absolute reduction of LVEF (n = 165). Patients were followed for EF and development of CTRCD (symptomatic EF reduction of >5% or >10% asymptomatic to <55%) over 1 year. RESULTS: Of 331 randomized patients, 2 died, and 22 withdrew consent or were lost to follow-up. Among 307 patients (age: 54 ± 12 years; 94% women; baseline LVEF: 59 ± 6%; GLS: -20.6 ± 2.4%) with a median (interquartile range) follow-up of 1.02 years (0.98 to 1.07 years), most (n = 278) had breast cancer. Heart failure risk factors were prevalent: 29% had hypertension, and 13% had diabetes mellitus. At the 1-year follow-up, although the primary outcome of change in LVEF was not significantly different between the 2 arms, there was significantly greater use of CPT, and fewer patients met CTRCD criteria in the GLS-guided than the EF-guided arm (5.8% vs. 13.7%; p = 0.02), and the 1-year EF was 57 ± 6% versus 55 ± 7% (p = 0.05). Patients who received CPT in the EF-guided arm had a larger reduction in LVEF at follow-up than in the GLS-guided arm (9.1 ± 10.9% vs. 2.9 ± 7.4%; p = 0.03). CONCLUSIONS: Although the change in LVEF was not different between the 2 arms as a whole, when patients who received CPT were compared, those in the GLS-guided arm had a significantly lower reduction in LVEF at 1 year follow-up. Furthermore, GLS-guided CPT significantly reduced a meaningful fall of LVEF to the abnormal range. The results support the use of GLS in surveillance for CTRCD. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).

Prognostic value of automated longitudinal strain measurements in asymptomatic aortic stenosis.

OBJECTIVE: Two-dimensional (2D) longitudinal strain (LS) predicts cardiac events in aortic stenosis (AS). However, it requires manual editing, which affects its accuracy and reliability. We investigated whether left ventricular (LV), left atrial (LA) and right ventricular (RV) LSs using fully automated 2D strain software provide useful prognostic information in asymptomatic AS. METHODS: We performed LS analyses in 340 asymptomatic patients with AS using novel, fully automated 2D strain analytical software (AutoStrain, Philips) to obtain LV global LS (LVGLS), LALS, RV free wall LS and RVLS. The primary end point was a composite of cardiac events, including cardiac death, heart failure hospitalisation, myocardial infarction or ventricular tachyarrhythmia. RESULTS: During a median of 24 months follow-up, 46 patients reached a primary end point. 62 patients had aortic valve surgery. All four LSs were significantly associated with the primary end point using univariate analysis (HR 0.821 to 0.951, p<0.05). Multivariate analysis revealed that LVGLS (HR 0.873 to 0.888, p<0.05) remained significantly associated with cardiac events, even after adjusting haemodynamic measures of AS severity and LV ejection fraction. Kaplan-Meier survival curve showed median values of both LVGLS (cut-off: 15.1%) and LALS (cut-off: 22.3%) provide a significant difference in cardiac event rate (3-year event-free rate; LVGLS: 89% vs 76%, p=0.002; LALS: 89% vs 76%, p=0.001). Classification and regression-tree analysis, including four LSs, clinical characteristics and traditional echocardiographic parameters, selected LVGLS and E/ε' for stratifying a high-risk group of patients with cardiac events. CONCLUSIONS: Fully automated 2D LS analysis, especially LVGLS provides useful prognostic information in asymptomatic AS.

Short-term exposure to ambient fine particulate matter and out-of-hospital cardiac arrest: a nationwide case-crossover study in Japan.

BACKGROUND: PM2·5 is an important but modifiable environmental risk factor, not only for pulmonary diseases and cancers, but for cardiovascular health. However, the evidence regarding the association between air pollution and acute cardiac events, such as out-of-hospital cardiac arrest (OHCA), is inconsistent, especially at concentrations lower than the WHO daily guideline (25 µg/m3). This study aimed to determine the associations between exposure to ambient air pollution and the incidence of OHCA. METHODS: In this nationwide case-crossover study, we linked prospectively collected population-based registry data for OHCA in Japan from Jan 1, 2014, to Dec 31, 2015, with daily PM2·5, carbon monoxide (CO), nitrogen dioxide (NO2), photochemical oxidants (Ox), and sulphur dioxide (SO2) exposure on the day of the arrest (lag 0) or 1-3 days before the arrest (lags 1-3), as well as the moving average across days 0-1 and days 0-3. Daily exposure was calculated by averaging the measurements from all PM2·5 monitoring stations in the same prefecture. The effect of PM2·5 on risk of all-cause or cardiac OHCA was estimated using a time-stratified case-crossover design coupled with conditional logistic regression analysis, adjusted for daily temperature and relative humidity. Single-pollutant models were also investigated for the individual gaseous pollutants (CO, NO2, Ox, and SO2), as well as two-pollutant models for PM2·5 with these gaseous pollutants. Subgroup analyses were done by sex and age. FINDINGS: Over the 2 years, 249 372 OHCAs were identified, with 149 838 (60·1%) presumed of cardiac origin. The median daily PM2·5 was 11·98 µg/m3 (IQR 8·13-17·44). Each 10 µg/m3 increase in PM2·5 was associated with increased risk of all-cause OHCA on the same day (odds ratio [OR] 1·016, 95% CI 1·009-1·023) and at lags of up to 3 days, ranging from OR 1·015 (1·008-1·022) at lag 1 to 1·033 (1·023-1·043) at lag 0-3. Results for cardiac OHCA were similar (ORs ranging from 1·016 [1·007-1·025] at lags 1 and 2 to 1·034 [1·021-1·047] at lag 0-3). Patients older than 65 years were more susceptible to PM2·5 exposure than younger age groups but no sex differences were identified. CO, Ox, and SO2 were also positively associated with OHCA while NO2 was not. However, in two-pollutant models of PM2·5 and gaseous pollutants, only PM2·5 (positive association) and NO2 (negative association) were independently associated with increased risk of OHCA. INTERPRETATION: Short-term exposure to PM2·5 was associated with an increased risk of OHCA even at relatively low concentrations. Regulatory standards and targets need to incorporate the potential health gains from continual air quality improvement even in locations already meeting WHO standards. FUNDING: None.

Patient Risk Factors for Bioprosthetic Aortic Valve Degeneration: A Systematic Review and Meta-Analysis.

The choice of valve type for aortic valve replacement surgery is sometimes challenging. The main risk for bioprostheses is structural valve degeneration (SVD); however, little is known about what the most important risk factors are. We conducted a systematic review and meta-analysis to identify the risk factors and estimate their pooled effect sizes to aid the prosthesis choice for replacement. We followed PRISMA guidelines and systematically searched three electronic databases (PubMed, Scopus, and Web of Science) using appropriate key terms: 'aortic valve', 'bioprosthesis', 'degeneration', 'durability', 'prosthesis failure', etc. Hazard ratio (HR) and odds ratio (OR) and associated 95% confidence intervals (CI) were extracted. Pooled risk estimates were calculated using a random-effects model. Twenty-nine (29) observational studies were included with a total of 25,490 patients, 981 of whom developed SVD over a mean follow-up time of 18.5 years. Four (4) factors influencing bioprosthetic SVD were identified: increasing age was a protective factor (per 1-yr increase, HR: 0.91 [95% CI 0.89, 0.94], p<0.0001), whereas increased body surface area (HR 1.77 [1.04, 3.01], p=0.034), patient-prosthesis mismatch (HR 1.95 [1.56, 2.43], p<0.001), and smoking (HR 2.28 [1.37, 3.79], p=0.0015) were risk factors for SVD. We found younger age, patient-prosthesis mismatch, body surface area, and smoking, as risk factors for aortic SVD, which should be considered for valve selection. This study generates a further hypothesis that accelerated flow across the valve is a shared key component in the pathophysiology of SVD, thus future research should consider other high cardiac output states.

Early life exposure to coal mine fire and tobacco smoke affect subclinical vascular function.

OBJECTIVE: To evaluate whether vascular health in young children was associated with exposure to a 6-week episode of coal mine fire smoke or environmental tobacco smoke (ETS) in a retrospective cohort study. METHODS: Three years after a coal mine fire in Victoria, Australia, we investigated the vascular health of children either in utero (n=75) or aged <2 years (postnatal exposure, n=96) at the time of the fire. The outcomes were the carotid intima-media thickness (IMT) and pulse wave velocity (PWV). The mean and peak daily particulate matter <2.5 µm in diameter (PM2.5) exposures were estimated based on their daily locations throughout the fire period. Multivariable linear regression models were used to test for associations between the fire-related PM2.5 and outcomes adjusted for relevant covariates including ETS. RESULTS: In the postnatal-exposure group, each 10 µg/m³ increase in mean PM2.5 level was independently positively associated with PWV (ß=0.116, p=0.028). When these two groups were combined, there was an association between mean PM2.5 and increased PWV in those children who had ETS exposure (ß=0.148, p=0.033) or whose mothers smoked (ß=0.151, p=0.011), but not in those not exposed to ETS or maternal smoking. CONCLUSIONS: Three years after a coal mine fire, infants aged up to 2 years at the time of exposure have increases in vascular stiffness. Although no adverse effects were observed in the in uterus exposure group, further follow-up study is needed to elucidate the long-term effects of coal mine fire smoke exposure.