Alcohol Abstinence in Drinkers with Atrial Fibrillation.

BACKGROUND: Excessive alcohol consumption is associated with incident atrial fibrillation and adverse atrial remodeling; however, the effect of abstinence from alcohol on secondary prevention of atrial fibrillation is unclear. METHODS: We conducted a multicenter, prospective, open-label, randomized, controlled trial at six hospitals in Australia. Adults who consumed 10 or more standard drinks (with 1 standard drink containing approximately 12 g of pure alcohol) per week and who had paroxysmal or persistent atrial fibrillation in sinus rhythm at baseline were randomly assigned in a 1:1 ratio to either abstain from alcohol or continue their usual alcohol consumption. The two primary end points were freedom from recurrence of atrial fibrillation (after a 2-week "blanking period") and total atrial fibrillation burden (proportion of time in atrial fibrillation) during 6 months of follow-up. RESULTS: Of 140 patients who underwent randomization (85% men; mean [±SD] age, 62±9 years), 70 were assigned to the abstinence group and 70 to the control group. Patients in the abstinence group reduced their alcohol intake from 16.8±7.7 to 2.1±3.7 standard drinks per week (a reduction of 87.5%), and patients in the control group reduced their alcohol intake from 16.4±6.9 to 13.2±6.5 drinks per week (a reduction of 19.5%). After a 2-week blanking period, atrial fibrillation recurred in 37 of 70 patients (53%) in the abstinence group and in 51 of 70 patients (73%) in the control group. The abstinence group had a longer period before recurrence of atrial fibrillation than the control group (hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.84; P = 0.005). The atrial fibrillation burden over 6 months of follow-up was significantly lower in the abstinence group than in the control group (median percentage of time in atrial fibrillation, 0.5% [interquartile range, 0.0 to 3.0] vs. 1.2% [interquartile range, 0.0 to 10.3]; P = 0.01). CONCLUSIONS: Abstinence from alcohol reduced arrhythmia recurrences in regular drinkers with atrial fibrillation. (Funded by the Government of Victoria Operational Infrastructure Support Program and others; Australian New Zealand Clinical Trials Registry number, ACTRN12616000256471.).

Myocardial fibrosis and arrhythmic burden in systemic sclerosis.

OBJECTIVES: Cardiac complications of SSc are a leading cause of SSc-associated death. Cardiac imaging for identifying substrate abnormality may be useful in predicting risk of cardiac arrhythmias or future cardiac failure. The aim of this study was to quantify the burden of asymptomatic fibro-inflammatory myocardial disease using cardiac magnetic resonance imaging (CMR) and assess the relationship between asymptomatic myocardial fibrosis and cardiac arrhythmias in SSc. METHODS: Thirty-two patients with SSc with no documented history of pulmonary vascular or heart disease underwent CMR with gadolinium and 24-h ambulatory ECG. Focal myocardial fibrosis was assessed using post-gadolinium imaging and diffuse fibro-inflammatory myocardial disease quantified using T1- and T2-mapping. CMR results were compared with an age- and sex-matched control group. RESULTS: Post-gadolinium focal fibrosis was prevalent in SSc but not controls (30% vs 0%, p < 0.01).. T1-mapping values (as a marker of diffuse fibrosis) were greater in SSc than controls [saturated recovery single-shot acquisition (SASHA): 1584 ms vs 1515 ms, P < 0.001; shortened Modified look locker sequence (ShMOLLI): 1218 ms vs 1138 ms, p < 0.001]. More than one-fifth (22.6%) of the participants had ventricular arrhythmias on ambulatory ECG, but no associations between focal or diffuse myocardial fibrosis and arrhythmias were evident. CONCLUSION: In SSc patients without evidence of overt cardiac disease, a high burden of myocardial fibrosis and arrhythmias was identified. However, there was no clear association between focal or diffuse myocardial fibrosis and arrhythmias, suggesting CMR may have limited use as a screening tool to identify SSc patients at risk of future significant arrhythmias.

Exercise cardiovascular magnetic resonance reveals reduced cardiac reserve in pediatric cancer survivors with impaired cardiopulmonary fitness.

BACKGROUND: Pediatric cancer survivors are at increased risk of cardiac dysfunction and heart failure. Reduced peak oxygen consumption (peak VO2) is associated with impaired cardiac reserve (defined as the increase in cardiac function from rest to peak exercise) and heart failure risk, but it is unclear whether this relationship exists in pediatric cancer survivors. This study sought to investigate the presence of reduced peak VO2 in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac haemodynamics and systolic function during exercise. METHODS: Twenty pediatric cancer survivors (8-24 years; 10 male) treated with anthracycline chemotherapy ± radiation underwent cardiopulmonary exercise testing to quantify peak VO2, with a value < 85% of predicted defined as impaired peak VO2. Resting cardiac function was assessed using 2- and 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate, stroke volume index (SVI) and cardiac index (CI) using exercise cardiovascular magnetic resonance (CMR). RESULTS: Twelve of 20 survivors (60%) had reduced peak VO2 (70 ± 16% vs. 97 ± 14% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired peak VO2. However, those with reduced peak VO2 had diminished cardiac reserve, with a lesser increase in CI and SVI during exercise (Interaction P < 0.01 for both), whilst the heart rate response was similar (P = 0.71). CONCLUSIONS: Whilst exercise intolerance is common among pediatric cancer survivors, it is poorly explained by resting measures of cardiac function. In contrast, impaired exercise capacity is associated with impaired haemodynamics and systolic functional reserve measured during exercise. Consequently, measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure.

Reduction in mortality from implantable cardioverter-defibrillators in non-ischaemic cardiomyopathy patients is dependent on the presence of left ventricular scar.

Aims: In patients with non-ischaemic cardiomyopathy (NICM), the mortality benefit of a primary prevention implantable cardioverter-defibrillator (ICD) has been challenged. Left ventricular (LV) scar identified by cardiac magnetic resonance (CMR) imaging is associated with a high risk of malignant arrhythmia in NICM. We aimed to determine the impact of LV scar on the mortality benefit from a primary prevention ICD in NICM. Methods and results: We recruited 452 consecutive heart failure patients [New York Heart Association (NYHA) Class II/III] with NICM and LV ejection fraction ≤35% from a state-wide CMR service. All patients fulfilled European Society of Cardiology guidelines for primary prevention ICD implantation; however, the decision to implant was at the treating physician's discretion. Baseline clinical and CMR data were recorded prospectively and heart failure mortality risk (MAGGIC score) was calculated. The primary study outcome measurement was all-cause mortality based on presence or absence of ICD, stratified by LV scar. Median follow-up was 37.9 months and there was no difference in MAGGIC score between those who did and did not receive a primary prevention ICD (19.30 ± 5.46 vs. 18.90 ± 5.67, P = 0.50). In patients without LV scar, ICD implantation was not associated with improved mortality [hazard ratio (HR) = 1.22, 95% confidence interval (CI): 0.53-2.78, P = 0.64]. In patients with LV scar, ICD implantation was independently associated with reduced mortality (HR = 0.45, 95% CI: 0.26-0.77, P = 0.003). Conclusions: In patients with NICM, primary prevention ICD implantation is only associated with reduced mortality in patients with LV scar. This may enable more effective selection of NICM patients for ICD implantation compared with current guidelines.

Clinical Utility of Stress Echocardiography in Remote Indigenous and Non-Indigenous Populations: A 10-Year Study in Central Australia.

BACKGROUND: Remote Central Australia has a large Indigenous population and a significant burden of cardiovascular disease. Stress echocardiography has been previously validated as a useful investigation for long-term prognostication. However, there are no prior studies assessing its utility in remote or Indigenous populations. METHOD: Consecutive individuals undergoing stress echocardiography in Central Australia between 2007 and 2017 were included. Stress echocardiography was performed and reported via standard protocols. Individuals were followed up for all-cause mortality. RESULTS: One-thousand and eight patients (1,008) (54% Indigenous Australian) were included. After a mean follow-up of 3.5±2.4 years, 54 (5%) patients were deceased. Overall, 797 (79%) patients had no abnormalities during rest or stress echocardiography, with no difference according to ethnicity (p>0.05). In patients with a normal test, annual mortality averaged 1.3% over 5 years of follow-up, with annual mortality significantly higher in Indigenous compared to non-Indigenous individuals (1.8% vs 0.6% respectively). In those with an abnormal test, annual mortality was 4.4% vs 1.3% in Indigenous and non-Indigenous individuals respectively. Increasing age, Indigenous ethnicity and cardiometabolic comorbidities were associated with mortality in univariate analyses (p<0.05 for all). In multivariate models, only chronic kidney disease remained predictive of mortality, with other associations (including Indigenous ethnicity) becoming attenuated. CONCLUSION: This is the first study to report on the use of stress echocardiography in a remote or Indigenous population. A normal stress echocardiogram in remote Indigenous individuals was able to identify a lower risk group of patients in this setting. Although Indigenous individuals with a normal test still had a higher annual rate of mortality compared to non-Indigenous individuals, this association appeared to be mediated by cardiometabolic comorbidities.

Comparison of Magnetic Resonance Analysis of Myocardial Scarring With Biomarker Release Following S-T Elevation Myocardial Infarction.

BACKGROUND: Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) is commonly assumed to represent myocardial fibrosis; however, comparative human histological data are limited, and there is no consensus on the most accurate method for LGE quantitation. We evaluated the relationship between CMR assessment of regional fibrosis and infarct size assessment using serial biomarkers after ST elevation acute myocardial infarction (STEMI). METHODS: Ninety-three patients treated for STEMI (59±10 years, 86% male) underwent CMR 6 months after infarction. Infarct size was quantified by CMR-LGE using manual and range of semi-automated thresholds (range: 2-10 standard deviations [SD]) above reference myocardium and the full width-half maximum (FWHM) technique, and compared with the rise in serum biomarkers. The agreement between CMR and biomarker in the identification of large infarcts based on peak troponin (TnI) levels was also analysed. RESULTS: Quantification methods had a strong influence on the infarct size assessment with CMR-LGE. Significant correlations were observed between LGE and biomarkers across all of the signal intensity thresholds. Whilst there was a wide variation with respect to the estimation of total LGE size (from 6.8±7.7 to 32.1±11.3 grams), the variation in the correlation with peak troponin level was much smaller (r-values ranging from 0.670 to 0.876). There was good agreement between CMR-LGE and biomarker assessment of infarct size; the best agreement between CMR-LGE and large infarction using a threshold of 8SD for peak TnI>50ng/mL (Cohen's kappa (κ)=0.722), and a threshold of 4SD for peak TnI >95ng/mL (κ=0.761). CONCLUSIONS: The correlation between CMR-LGE quantification of infarct size and biomarker release following STEMI at a range of semi-automated thresholds was consistently strong, with good agreement between measures across a range of thresholds.

Absence of late gadolinium enhancement on cardiac magnetic resonance imaging in ventricular fibrillation and nonischemic cardiomyopathy.

INTRODUCTION: Cardiac magnetic resonance (CMR)-identified late gadolinium enhancement (LGE), representing regional fibrosis, is often used to predict ventricular arrhythmia risk in nonischemic cardiomyopathy (NICM). However, LGE is more closely correlated with sustained monomorphic ventricular tachycardia (SMVT) than ventricular fibrillation (VF). We characterized CMR findings of ventricular LGE in VF survivors. METHODS: We examined consecutively resuscitated VF survivors undergoing contrast-enhanced 1.5T CMR between 9/2007 and 7/2016. We excluded coronary artery disease, hypertrophic cardiomyopathy, amyloid, sarcoid, arrhythmogenic right ventricular cardiomyopathy, and channelopathy. Preexisting implantable cardioverter-defibrillator (ICD) was a CMR contraindication. VF patients were divided into three groups: (1) NICM, (2) left ventricular (LV) dilatation with normal LV ejection fraction (LVEF), and (3) normal LV size and LVEF. Two groups of NICM patients with and without SMVT were examined for comparison. RESULTS: We analyzed 87 VF patients, and found that LGE was seen in 8/22 (36%) with NICM (LVEF 38 ± 11%, LV end-diastolic volume index [LVEDVI] 134 ± 68 mL/BSA), 11/40 (28%) with LV dilatation and normal LVEF (LVEDVI 103 ± 17 mL/BSA), 4/25 (16%) with normal LV size and LVEF. Incidence of LGE in NICM patients without prior ventricular tachycardia/VF (LVEF 36 ± 12%, LVEDVI 141 ± 46 mL/body surface area [BSA]) was 117/277 and was not lower than those with VF and NICM (42% vs 36%; P = 0.59). By contrast, 22/37 NICM patients with SMVT (LVEF 42 ± 11%, LVEDVI 123 ± 48 mL/BSA) were LGE-positive (59% NICM-SMVT vs 36% NICM-VF; P = 0.04). CONCLUSION: Most VF survivors with a diagnosis of NICM did not have LGE on CMR and would not have met primary prevention ICD criteria based on LVEF. Absence of LGE may not portend a benign prognosis in NICM. Novel strategies for determining SCD risk in this cohort are required.

Comparison of Pressure vs Volume Overload Ventricular Wall Stress in Patients With Valvular Heart Disease.

BACKGROUND: Aortic stenosis (AS) and mitral regurgitation (MR) result in different patterns of left ventricular remodeling and hypertrophy. OBJECTIVES: We characterized left ventricular wall stress (LVWS) profiles in pressure and volume-overloaded systems, examined the relationship between baseline LVWS and cardiac remodeling, and assessed the acute effects of valve intervention on LVWS using invasive pressures combined with cardiac magnetic resonance (CMR) imaging measures of left ventricular volumes/mass. METHODS: A total of 47 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) and 15 patients with severe MR undergoing MitraClip (MC) underwent a 6-minute walk test (6MWT), transthoracic echocardiogram, and CMR before their procedures. Catheters in the left ventricle were used to record hemodynamic changes before and after valve/clip deployment. This was integrated with CMR data to calculate LVWS before and after intervention. RESULTS: The TAVR group demonstrated significant reductions in systolic LVWS post procedure (median 24.7 Pa [IQR: 14 Pa] pre vs median 17.3 Pa [IQR: 12 Pa] post; P < 0.001). The MC group demonstrated significant reductions in diastolic LVWS (median 6.4 Pa [IQR: 5 Pa] pre vs median 4.3 Pa [IQR: 4.1 Pa] post; P = 0.021) with no significant change in systolic LVWS (30.6 ±1.61 pre vs 33 ±2.47 Pa post; P = 0.16). There was an inverse correlation between baseline systolic LVWS and 6MWT in the TAVR group (r = -0.31; P = 0.04). CONCLUSIONS: TAVR results in significant reductions in systolic LVWS acutely. MC results in significant reductions in diastolic LVWS. Higher baseline systolic LVWS in TAVR is associated with shorter 6MWT suggesting that in AS, LVWS may be a useful marker of early decompensation.

Assessing atrial myopathy with cardiac magnetic resonance imaging in embolic stroke of undetermined source.

BACKGROUND: Left atrial myopathy has been implicated in atrial fibrillation (AF)-related stroke and embolic stroke of undetermined source (ESUS). OBJECTIVE: To use advanced cardiac magnetic resonance (CMR) imaging techniques, including left atrial (LA) strain and 4D flow CMR, to identify atrial myopathy in patients with ESUS. METHODS: 20 patients with ESUS and no AF or other cause for stroke, and 20 age and sex-matched controls underwent CMR with 4D flow analysis. Markers of LA myopathy were assessed including LA size, volume, ejection fraction, and strain. 4D flow CMR was performed to measure novel markers of LA stasis such as LA velocities and the LA residence time distribution time constant (RTDtc). These markers of LA myopathy were compared between the two groups. RESULTS: There was no significant difference in: CMR-calculated LA velocities or LA total, passive or active ejection fractions between the groups. There was no significant difference in CMR-derived reservoir, conduit or contractile average longitudinal strain between the ESUS and control groups (22.9 vs 22.6%, p=0.379, 11.2 ± 3.5 vs 12.4 ± 2.6% p=0.224, 10.8 ± 3.2 vs 10.4 ± 2.3%, p=0.625 respectively). Similarly, RTDtc was not significantly longer in ESUS patients compared to controls (1.3 ± 0.2 vs 1.2 ± 0.2, p=0.1). CONCLUSIONS: There were no significant differences in any CMR marker of atrial myopathy in ESUS patients compared to healthy controls, likely reflecting the multiple possible aetiologies of ESUS suggesting that the role LA myopathy plays in ESUS is smaller than previously thought.

Disease specific determinants of cardiopulmonary fitness in systemic sclerosis.

OBJECTIVES: We aimed to quantify the burden of exercise intolerance in systemic sclerosis (SSc) and explore the disease features that contribute to impaired exercise capacity (measured as peak oxygen uptake, peak VO2) to provide novel mechanistic insights into the causes of physical disability in SSc. METHODS: Thirty-three SSc patients with no history of cardiac disease and no active myositis underwent cardiac and skeletal muscle MRI, transthoracic echocardiography, pulmonary function tests and cardiopulmonary exercise testing (CPET). CPET results were compared to an age-, sex-, and weight-matched controls with no overt cardiopulmonary disease. Native T1 and T2-mapping sequences were used to quantify diffuse fibroinflammatory myocardial disease and qualitative assessment of skeletal muscle oedema was performed. The associations between parameters of cardiorespiratory function and skeletal muscle abnormalities and peak VO2 were evaluated with linear regression analysis. RESULTS: Exercise capacity was markedly impaired in SSc and significantly reduced when compared to control subjects (percent predicted peak VO2: 70% vs 98%, p < 0⋅01). Diffuse myocardial fibroinflammatory disease (p < 0⋅01) and skeletal muscle oedema (p = 0⋅01) were significantly associated with reduced exercise capacity. There was no association between impaired exercise capacity and left ventricular ejection fraction. CONCLUSION: SSc is associated with marked functional impairment that is not explained by commonly used parameters of cardiac function such as left ventricular ejection fraction. Rather, only more sensitive measures of organ involvement are associated with impaired exercise tolerance. Our results show diffuse interstitial changes of the myocardium and skeletal muscle affect oxygen uptake and are important contributors to functional limitation in SSc.

Too Little of a Good Thing: Strong Associations Between Cardiac Size and Fitness Among Women.

BACKGROUND: Cardiorespiratory fitness (CRF) is associated with functional impairment and cardiac events, particularly heart failure (HF). However, the factors predisposing women to low CRF and HF remain unclear. OBJECTIVES: This study sought to evaluate the association between CRF and measures of ventricular size and function and to examine the potential mechanism linking these factors. METHODS: A total of 185 healthy women aged >30 years (51 ± 9 years) underwent assessment of CRF (peak volume of oxygen uptake [Vo2peak]) and biventricular volumes at rest and during exercise by using cardiac magnetic resonance (CMR). The relationships among Vo2peak, cardiac volumes, and echocardiographic measures of systolic and diastolic function were assessed using linear regression. The effect of cardiac size on cardiac reserve (change in cardiac function during exercise) was assessed by comparing quartiles of resting left ventricular end-diastolic volume (LVEDV). RESULTS: Vo2peak was strongly associated with resting measures of LVEDV and right ventricular end-diastolic volume (R2 = 0.58-0.63; P < 0.0001), but weakly associated with measures of resting left ventricular (LV) systolic and diastolic function (R2 = 0.01-0.06; P < 0.05). Increasing LVEDV quartiles were positively associated with cardiac reserve, with the smallest quartile showing the smallest reduction in LV end-systolic volume (quartile [Q]1: -4 mL vs Q4: -12 mL), smallest augmentation in LV stroke volume (Q1: +11 mL vs Q4: +20 mL) and cardiac output (Q1: +6.6 L/min vs Q4: +10.3 L/min) during exercise (interaction P < 0.001 for all). CONCLUSIONS: A small ventricle is strongly associated with low CRF because of the combined effect of a smaller resting stroke volume and an attenuated capacity to increase with exercise. The prognostic implications of low CRF in midlife highlight the need for further longitudinal studies to determine whether women with small ventricles are predisposed to functional impairment, exertional intolerance, and HF later in life.

Using magnetic resonance imaging to map the hidden burden of muscle involvement in systemic sclerosis.

BACKGROUND: Skeletal muscle can be directly affected by systemic sclerosis (SSc); however, a significant burden of SSc-associated myopathy is undetected because clinical parameters such as weakness and creatine kinase (CK) are unreliable biomarkers of muscle involvement. This study presents qualitative and quantitative magnetic resonance imaging (MRI) findings that quantify the prevalence of myopathy and evaluate any association between skeletal and cardiac muscle involvement in SSc. METHODS: Thirty-two patients with SSc who fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria underwent skeletal muscle MRI in addition to cardiac MRI. Skeletal muscles were independently assessed by two musculoskeletal radiologists for evidence of oedema, fatty infiltration and atrophy. Skeletal muscle T2 mapping times and percentage fat fraction were calculated. Linear regression analysis was used to evaluate the clinical and myocardial associations with skeletal muscle oedema and fatty infiltration. Cardiac MRI was performed using post gadolinium contrast imaging and parametric mapping techniques to assess focal and diffuse myocardial fibrosis. RESULTS: Thirteen participants (40.6%) had MRI evidence of skeletal muscle oedema. Five (15.6%) participants had fatty infiltration. There was no association between skeletal muscle oedema and muscle strength, creatine kinase, inflammatory markers or fibroinflammatory myocardial disease. Patients with skeletal muscle oedema had higher T2-mapping times; there was a significant association between subjective assessments of muscle oedema and T2-mapping time (coef 2.46, p = 0.02) and percentage fat fraction (coef 3.41, p = 0.02). Diffuse myocardial fibrosis was a near-universal finding, and one third of patients had focal myocardial fibrosis. There was no association between skeletal myopathy detected by MRI and burden of myocardial disease. CONCLUSIONS: MRI is a sensitive measure of muscle oedema and systematic assessment of SSc patients using MRI shows that myopathy is highly prevalent, even in patients without symptoms or other signs of muscle involvement. Similarly, cardiac fibrosis is highly prevalent but occurs independently of skeletal muscle changes. These results indicate that novel quantitative MRI techniques may be useful for assessing sub-clinical skeletal muscle disease in SSc.

Differentiating Nonischemic Dilated Cardiomyopathy With Incidental Infarction From Ischemic Cardiomyopathy by Geometric Indices Derived From Cardiovascular Magnetic Resonance.

PURPOSE: The purpose of this study was to differentiate nonischemic dilated cardiomyopathy with incidental myocardial infarction (NICM with incidental MI) from ischemic cardiomyopathy (ICM) by integrating left ventricular (LV) geometric indices and ischemic late gadolinium enhancement (LGE), obtained from cardiac magnetic resonance (CMR) imaging. MATERIALS AND METHODS: All subjects were studied on a 1.5 Tesla magnetic resonance imaging scanner. All patients had an LV ejection fraction (LVEF) <50% with LV dilation. LV end-diastolic volume (LVEDV), LVEDV index (LVEDVi), LVEF, the number and distribution of ischemic LGE segments, and ratios of volumetric and functional indices to ischemic LGE segments were determined. Logistic regression was used to detect the independent predictor of ICM. Receiver operating characteristic analysis differentiated NICM with incidental MI from ICM. RESULTS: Of a total of 63 patients enrolled, 45 patients had ICM, and 18 patients had NICM with incidental MI. Both groups had similar LVEF. Compared with ICM, NICM with incidental MI had more LV dilation, whereas ICM had more ischemic LGE segments. A higher number of ischamic LGE segments remained an independent predictor of ICM (odds ratio: 18.2, 95% confidence interval: 1.64-201.34, P=0.018). The optimal cut-off value for detecting NICM with incidental MI is the ratio of LVEDVi to the number of ischemic LGE segments over 25 mL/m2/segment (sensitivity 100%, specificity 91%, P<0.0001). CONCLUSION: Patients with NICM with incidental MI can be reliably distinguished from ICM using the ratio of LVEDVi divided by the number of ischemic LGE segments. This technique may improve diagnosis and help aid management of patients with cardiomyopathy and coexistent coronary artery disease.

Traditional markers of cardiac toxicity fail to detect marked reductions in cardiorespiratory fitness among cancer patients undergoing anti-cancer treatment.

AIMS: Left ventricular ejection fraction (LVEF) is standard of care for evaluating chemotherapy-associated cardiotoxicity, although global longitudinal strain (GLS) offers advantages. However, neither change in LVEF or GLS has been associated with short-term symptoms, functional capacity, or long-term heart failure (HF) risk. We sought to determine whether an integrative measure of cardiovascular function (VO2peak) that is strongly associated with HF risk would be more sensitive to cardiac damage induced by cancer treatment than LVEF, GLS, or cardiac biomarkers. METHODS AND RESULTS: Patients (n = 206, 53 ± 13 years, 35% male) scheduled to commence anti-cancer treatment completed assessment prior to, and within 6 months after therapy. Changes in echocardiographic measures of LV function (LVEF, GLS), cardiac biomarkers (troponin and BNP), and cardiorespiratory fitness (VO2peak) were measured. LV function was normal prior to treatment (LVEF 61 ± 5%; GLS -19.4 ± 2.1), but VO2peak was only 88 ± 26% of age-predicted. After treatment, VO2peak was reduced by 7 ± 15% (equivalent of 7 years normal ageing, P < 0.0001) and the rates of functional disability (defined as VO2peak ≤ 18 mL/min/kg) almost doubled (15% vs. 26%, P = 0.016). In contrast, small, reductions in LVEF (59 ± 5% vs. 58 ± 5%, P = 0.03) and GLS (-19.4 ± 2.1 vs. -18.9 ± 2.2, P = 0.002) and an increase in troponin levels (4.0 ± 6.9 vs. 26.4 ± 26.2 ng/mL, P < 0.0001) were observed. CONCLUSION: Anti-cancer treatment is associated with marked reductions in functional capacity that occur independent of reductions in LVEF and GLS. The assessment of VO2peak prior to, and following treatment may be a more sensitive means of identifying patients at increased risk of HF.

Prognostic value of coronary artery calcium scoring and computed tomography coronary angiography in remote Indigenous and non-Indigenous Australians.

BACKGROUND: The long-term prognostic utility of coronary calcification and coronary artery disease on computed tomography coronary angiography (CTCA) in remote Indigenous and non-Indigenous Australians is not known. METHODS: Consecutive patients undergoing CTCA from 2013 to 2017 in Central Australia were followed-up for major adverse cardiovascular events (MACE). RESULTS: 347 patients were included (50 ± 12 years; 47% female; 39% Indigenous). 172 (50.0%) exhibited coronary calcification. CTCA demonstrated no coronary artery disease (CAD) in 137 (39.5%), non-obstructive CAD in 149 (42.9%), and obstructive CAD in 61 (17.6%) patients. Although Indigenous ethnicity was associated with coronary calcification and baseline CAD in age- and gender-adjusted models, this association was non-significant after accounting for comorbidities. Over 4.6 years (IQR 3.52-5.68) of follow-up, MACE incidence rates per 100 person-years were 2.92 (CI 1.92-4.44) and 0.48 (CI 0.18-1.27) in those with and without calcification respectively (p = 0.001), and 0.15 (CI 0.02-1.09), 1.32 (CI 0.69-2.54), and 6.23 (CI 3.81-10.16) in patients with no, non-obstructive, and obstructive CAD respectively (p < 0.001). Coronary calcification and obstructive CAD were associated with 5-fold (HR 5.25, 95% CI 1.66-16.59, p = 0.005) and 6-fold (HR 6.35, 95% CI 2.70-14.89, p < 0.001) greater hazards of MACE respectively in multivariable models, with no significant interaction by ethnicity in these associations seen. CONCLUSIONS: The prognostic value of coronary calcification and CAD on CTCA amongst remote Indigenous individuals appears similar to that seen in non-Indigenous populations. Our data suggest that coronary artery calcium scoring and CTCA can be used to risk-stratify in remote settings where a normal study is associated with an excellent prognosis for at least two years.

Left atrial, pulmonary vein, and left atrial appendage anatomy in Indigenous individuals: Implications for atrial fibrillation.

BACKGROUND: Indigenous Australians experience a greater burden of AF. Whether this is in-part due to differences in arrhythmogenic structures that appear to contribute to AF differences amongst other ethnicities is not known. METHODS: We studied forty individuals matched for ethnicity and other AF risk factors. Computed tomography imaging was used to characterise left atrial (LA), pulmonary vein (PV), and left atrial appendage (LAA) anatomy. RESULTS: There were no significant differences in LA diameters or volumes between Indigenous and non-Indigenous Australians. Similarly, we could not detect any consistent differences in PV number, morphology, diameters, or ostial characteristics according to ethnicity. LAA analyses suggested that Indigenous Australians may have a greater proportion of non chickenwing LAA type, and a tendency for eccentric, oval-shaped LAA ostia; however, there were no other differences seen with regards to LAA volume or depth. Indexed values for LA, PV and LAA anatomy corrected for body size were broadly similar. CONCLUSIONS: In a cohort of individuals matched for AF risk factors, we could find no strong evidence of ethnic differences in LA, PV, and LAA characteristics that may explain a predisposition of Indigenous Australians for atrial arrhythmogenesis. These findings, in conjunction with our previous data showing highly prevalent cardiometabolic risk factors in Indigenous Australians with AF, suggest that it is these conditions that are more likely responsible for the AF substrate in these individuals. Continued efforts should therefore be directed towards risk factor management in an attempt to prevent and minimise the effects of AF in Indigenous Australians.

Measuring atrial stasis during sinus rhythm in patients with paroxysmal atrial fibrillation using 4 Dimensional flow imaging: 4D flow imaging of atrial stasis.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) is associated with cardioembolic risk, however events may occur during sinus rhythm (SR). 4D-flow cardiac magnetic resonance (CMR) imaging allows visualisation of left atrial blood flow, to determine the residence time distribution (RTD), an assessment of atrial transit time. OBJECTIVE: To determine if atrial transit time is prolonged in PAF patients during SR, consistent with underlying atrial stasis. METHOD: 91 participants with PAF and 18 healthy volunteers underwent 4D flow analysis in SR. Velocity fields were produced RTDs, calculated by seeding virtual 'particles' at the right upper pulmonary vein and counting them exiting the mitral valve. An exponential decay curve quantified residence time of particles in the left atrium, and atrial stasis was expressed as the derived constant (RTDTC) based on heartbeats. The RTDTC was evaluated within the PAF group, and compared to healthy volunteers. RESULTS: Patients with PAF (n = 91) had higher RTDTC compared with gender-matched controls (n = 18) consistent with greater atrial stasis (1.68 ±â€¯0.46 beats vs 1.51 ±â€¯0.20 beats; p = .005). PAF patients with greater thromboembolic risk had greater atrial stasis (median RTDTC of 1.72 beats in CHA2DS2-VASc≥2 vs 1.52 beats in CHA2DS2-VASc<2; p = .03), only female gender and left ventricular ejection fraction contributed significantly to the atrial RTDTC (p = .006 and p = .023 respectively). CONCLUSIONS: Atrial stasis quantified by 4D flow is greater in PAF, correlating with higher CHA2DS2-VASc scores. Female gender and systolic dysfunction are associated with atrial stasis. RTD offers an insight into atrial flow that may be developed to provide a personalised assessment of thromboembolic risk.

Epicardial and subcutaneous adipose tissue in Indigenous and non-Indigenous individuals: Implications for cardiometabolic diseases.

BACKGROUND: Obesity is prevalent in Indigenous populations who exhibit significant differences in body fat composition. While excess regional adiposity can be partially inferred from clinical measurements, noninvasive imaging allows for direct quantification of specific fat depots. Epicardial fat is a visceral adipose tissue that has been strongly associated with cardiometabolic disease in other populations. However, this ectopic fat depot has yet to be characterized in Indigenous populations. METHODS: We studied 100 individuals matched for ethnicity (Indigenous Australian and Caucasian descent), age, gender, and body mass index. Epicardial and subcutaneous adipose tissue volumes was quantified with computed tomography. Associations of ethnicity and adiposity measures were assessed using linear regression. RESULTS: Indigenous individuals had significantly greater epicardial fat volumes compared to non-Indigenous individuals (95.8±37.5 vs 54.1±27.6cm3, p<0.001). In contrast, subcutaneous fat volumes were comparable in Indigenous compared to non-Indigenous individuals (22.1±15.1 vs 20.3±13.5cm3, p=0.54). Sequential adjustment for age, gender, comorbidities, biochemical parameters, and medication use did not attenuate the association between Indigenous ethnicity and greater epicardial fat volume in multivariable models (B=43.0, p<0.001). Furthermore, this association did not materially change with the inclusion of various adiposity measures, such as body mass index, subcutaneous adipose tissue, or weight. CONCLUSIONS: Indigenous individuals have significantly greater epicardial fat, but similar subcutaneous fat volumes, compared to non-Indigenous individuals. This finding extends previous observations on body fat composition differences in these individuals, and supports the possibility that epicardial fat and other visceral adipose depots may be contributing to the greater burden of cardiovascular disease in Indigenous populations.

Relation of Alcohol Consumption to Left Ventricular Fibrosis Using Cardiac Magnetic Resonance Imaging.

Light-to-moderate regular alcohol consumption has been associated with reduced mortality, heart failure, and sudden death, with a well described "U-shaped" relationship. We sought to determine whether markers of diffuse ventricular fibrosis as assessed by cardiac magnetic resonance imaging (CMR) T1 mapping differ between nondrinkers and regular drinkers. We prospectively recruited 165 participants to undergo 3T CMR ventricular T1 mapping which included 120 regular light-to-moderate drinkers (7 to 28 standard drinks per week for >12 months) and 45 age and gender-matched nondrinking controls (1 standard drink ∼12 g alcohol). Diffuse ventricular fibrosis was assessed using ShMOLLI T1 mapping sequences performed in mid-short axis. Native T1, postcontrast T1 times and extracellular volume were compared in the left ventricle between regular drinkers and lifelong nondrinkers. In total 165 participants (mean age 59 ± 12 years, 70% male, 36% hypertension, mean LVEF 58 ± 11%) underwent CMR. Moderate alcohol intake (mean alcohol intake 16 ± 6 SDs/week) was associated with lower markers of diffuse ventricular fibrosis: native T1 time 1140 ± 47 vs 1173 ± 39 ms, p < 0.001; postcontrast T1 time 470 ± 47 vs 445 ± 43 ms, p = 0.01; extracellular volume 25.0 ± 2.7% vs 27.0 ± 2.8%, p = 0.003 despite similar LV size (p = 0.55) and mass compared with nondrinkers (p = 0.78). Quantity of alcohol intake and beverage type did not predict lower native T1 times. In conclusion, light-to-moderate or "social" alcohol consumption is associated with T1 changes on CMR suggestive of a reduction in diffuse ventricular fibrosis. These preliminary findings may provide some insights into the association between modest alcohol intake and reduction in sudden death and heart failure.