Cardiovascular Risk Factors and Disparities in Management of Embolic Stroke: A Western Sydney Perspective.

BACKGROUND: Ischaemic stroke remains one of the leading causes of death and disability worldwide. The population of Western Sydney has a unique demographic with lower socioeconomic status and a culturally and linguistically diverse population. This study aims to investigate the demographics and cardiovascular risk factors of patients in Western Sydney, focusing on the prevalence and profile of cardioembolic (CE) strokes and embolic strokes of undetermined source (ESUS). METHOD: Prospective data were collected in 463 patients with ischaemic stroke presenting to a tertiary centre in Western Sydney, who underwent predischarge transthoracic echocardiography. Patients with haemorrhagic strokes or unclear stroke diagnosis were excluded. Analysis of stroke subtype (CE, ESUS, or non-embolic) and clinical characteristics was performed based on age, gender, and prior atrial fibrillation (AF) prevalence. RESULTS: Of the 463 patients, 147 (32%) had CE strokes, and 147 (32%) had ESUS. Cardioembolic (CE) strokes were associated with older age (≥65 years) and a history of congestive cardiac failure. Older patients had higher rates of hypertension, ischaemic heart disease, AF, and congestive heart failure. History of AF was present in 67 patients (14.5%); however, only 51% received anticoagulation before admission despite a low bleeding risk. The transthoracic echocardiography characteristics of ESUS/non-embolic strokes differed from those of CE strokes; 20% of patients with ESUS had an enlarged left atrium, suggesting a subset of patients with ESUS with a left atrial myopathy. CONCLUSIONS: Patients with ischaemic stroke in Western Sydney have a high prevalence of cardiovascular risk factors which were often undertreated. Half of the patients with prior AF did not receive anticoagulation despite low bleeding risk, indicating a gap in optimal stroke prevention. There were distinct echocardiographic characteristics among stroke subtypes. Further analysis of left atrium parameters may provide greater insights into the pathogenesis and prevention of embolic strokes.

Alterations in Left Atrial Strain in Breast Cancer Patients Immediately Post Anthracycline Exposure.

AIMS: With improved diagnosis and treatments, a greater percentage of breast cancer patients are achieving long-term survival. Consequently, long-term cardiotoxicity secondary to chemotherapy has become more prevalent, warranting improved cardiac surveillance. We evaluated changes in left atrial (LA) strain in breast cancer patients immediately post anthracycline (AC) therapy to assess its utility as a marker of diastolic dysfunction. METHODS: This was a prospective cohort study of 128 consecutive human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who underwent transthoracic echocardiography prior to and immediately post AC treatment. Traditional left ventricular (LV) systolic and diastolic parameters and LA volumes were evaluated; additionally, LV global longitudinal strain (LV GLS) and LA phasic strain were measured. RESULTS: All patients had normal LV ejection fraction (>53%) post AC, though LV GLS was significantly reduced. Peak E and é velocities were reduced post AC, with no change in LA volumes. LA reservoir strain (LASRES 34.8% vs 31.5%, p<0.001) and conduit strain (LASCD 17.2% vs 14.4%, p<0.001) were significantly lower post AC and correlated modestly with LV diastolic parameters. Reduction in LA strain post AC was evident even in patients with preserved LV systolic and diastolic function. More patients demonstrated alteration in diastolic function (≥15% reduction in LASRES from baseline) (32%) compared to alteration in systolic function (≥15% reduction in LV GLS) (23%). CONCLUSIONS: LA strain is a promising marker of early diastolic dysfunction. We demonstrate its potential utility in surveillance of breast cancer patients treated with AC.

Changes in left atrial phasic strain and mechanical dispersion: Effects of age and gender.

PURPOSE: Left atrial (LA) function by two-dimensional (2D) strain is an emerging tool with increasing clinical utility. Age and gender are key modulators of strain parameters; however, the specific time course for LA structural and functional changes is not clearly defined. METHODS: A total of 147 healthy individuals (20-69 years) underwent transthoracic echocardiography; subjects were evaluated by age (decade) and gender. LA and left ventricular (LV) volumetric and strain measurements were performed. RESULTS: Left atrial reservoir (ƐR) and conduit strain (ƐCD) with negatively correlated with age (r =-.36; r = -.56; P < .001, respectively) being significantly lower by the 6th and 5th decades, respectively. Contractile strain (ƐCT) positively correlated with age (r = .36; P < .001), being significantly higher by the 6th decade. ƐR and ƐCD were higher in young females (20-34 years) compared to young males (P = .033 and P < .001, respectively). ƐCT was significantly higher in middle-aged adult males (35-50yrs; P = .010), though seen later in females (≥51 years; P = .005). Standard deviation of time to positive strain (SD-TPS) significantly higher by the 5th decade and correlated with age in both males (r = .44; P <.001) and females (r = .40; P = .001). CONCLUSION: We demonstrate that ƐR and ƐCD are lower with age, with differing rates between males and females. As a compensatory mechanism for decline in ƐCD, ƐCT is higher, more notably in males; comparatively, females display a more prominent decline in ƐR and ƐCD with age. Alteration in electromechanical properties occurred in both genders with SD-TPS becoming higher with age.

Redefining anthracycline-related subclinical cardiotoxicity: 'Absolute' and 'relative' change in longitudinal strain.

AIMS: Anthracycline chemotherapy (AC) for breast cancer can cause cancer therapy-related cardiac dysfunction (CTRCD) with resultant heart failure, traditionally defined as a reduction in left ventricular (LV) ejection fraction on echocardiography. In recent years, global longitudinal systolic strain (GLS) has been used to identify subclinical cardiac dysfunction prior to development of overt CTRCD. Recent harmonized guidelines have incorporated GLS into definitions for CTRCD to identify cardiac dysfunction and inform decisions regarding cardioprotective strategies. METHODS AND RESULTS: We evaluated subclinical dysfunction in breast cancer patients treated with AC and determined the echocardiographic and patient factors associated with significant GLS changes. One hundred fourteen HER2 negative patients treated with AC were prospectively recruited and underwent serial echocardiograms (LVEF and LVGLS) at three time points (prior to AC, 3 months, and 1 year). CTRCD was defined as an asymptomatic reduction in LVEF of 10% or symptomatic drop of 5% to LVEF <53%. Subclinical LV dysfunction was defined as a reduction of ≥10% in GLS compared with baseline, recognizing that this cut off identified an 'at risk cohort' rather than patients with established CTRCD. No participant demonstrated CTRCD by reduction in LVEF. Forty-three patients (38%) demonstrated a ≥10% relative reduction in GLS at 12 months; 20/43 (47%) had a reduced absolute GLS to <16%, and were older, had hypertension, increased LV mass, lower baseline e' velocity and GLS. GLS ≥20.5% at baseline yielded a sensitivity of 79% and specificity of 87% for a normal GLS (i.e., ≥16%) at 1 year despite a ≥10% reduction from baseline. CONCLUSIONS: We present a stepwise evaluation for subclinical LV dysfunction using both a relative reduction in GLS combined with an absolute reduction in GLS. We believe our findings may re-stratify patients with a high baseline GLS into a lower risk group despite transient relative GLS decrements ≥10%.

Left atrial mechanics evaluated by two-dimensional strain analysis: alterations in essential hypertension.

BACKGROUND: Hypertension is a cardiovascular risk factor that predisposes to cardiac structural alterations namely increased left ventricular (LV) wall thickness, reduced LV compliance and diastolic dysfunction, with consequent left atrial (LA) dilation and functional impairment. In this article, we evaluated differences in left atrial structure and function using two-dimensional speckle tracking echocardiography in patients with hypertension compared with controls. METHODS: This was a retrospective cross-sectional study of 208 hypertensive patients and 157 controls who underwent a comprehensive transthoracic echocardiogram. Patients with hypertension were stratified by the presence of left ventricular hypertrophy (LVH). RESULTS: Non-LVH hypertension patients had lower left atrial reservoir strain (LAS RES ) (34.78 ±â€Š29.78 vs. 29.78 ±â€Š6.08; P  = 0.022) and conduit strain (LAS CD ) (19.66 ±â€Š7.29 vs. 14.23 ±â€Š4.59; P  = 0.014) vs. controls despite similar left atrial volumes (LAV) . Left atrial contractile strain (LAS CT ) was not significantly different between non-LVH hypertension patients and controls (15.12 ±â€Š3.77 vs. 15.56 ±â€Š3.79; P  = 0.601). Left atrial mechanical dispersion was significantly higher in the LVH group compared with the non-LVH hypertension group (42.26 ±â€Š13.01 vs. 50.06 ±â€Š14.95; P  = 0.009). In multivariate regression analysis, LVH correlated with left atrial mechanical dispersion ( P  = 0.016). An age-hypertension interaction independently correlated with LAS CT ( P  < 0.001). CONCLUSION: Hypertension results in functional left atrial changes even before development of LV hypertrophy and structural left atrial changes with increased left atrial volume. We demonstrate both a likely hypertension-associated left atrial myopathy that prevents age-related compensatory increase in left atrial contractile function, and impact of LVH in hypertension on left atrial dyssynchrony.

Diagnostic and prognostic value of the left atrial myopathy evaluation in cardiac amyloidosis using echocardiography.

BACKGROUND: Cardiac amyloidosis (CA) is an under-recognized cause of heart failure. Left atrial (LA) myopathy contributes to a worse prognosis in heart failure and is a feature of transthyretin (ATTR) and light-chain (AL) CA. LA mechanical dispersion (LA-MD) is a novel marker of intra-atrial dyssynchrony implicated in LA myopathy and the future development of atrial fibrillation (AF). AIMS: This study aimed to determine the characteristics and prognostic value of LA myopathy in ATTR and AL cardiomyopathy through a comprehensive LA echocardiographic evaluation. METHODS: ATTR (n = 86) and AL (n = 86) CA patients were compared with hypertensive heart disease (HHT) patients (n = 58). Transthoracic echocardiographic measurements including LA strain and LA-MD were obtained with patient follow-up for mortality. RESULTS: ATTR and AL patients had a median follow-up of 66 months, with 26 mortality events. Left ventricular (LV) mass, diastolic function (average-e' and E/e'), LV global longitudinal strain, and LA volume and function (LA function index and strain) were more impaired in ATTR versus AL; these echocardiographic parameters were more impaired in both amyloid groups compared to HHT patients (P < 0.05). LA-MD was increased in ATTR versus AL [median 72.2 (inter-quartile range 55-88.9) vs. 54 (43.5-64.2), respectively, P < 0.001]. Multivariable logistic regression adjusted for age, presence of AF, LV mass, global and basal strain, and E/e' demonstrated that LA-MD was an independent determinant of ATTR CA (P = 0.014). On multivariable analysis, LA reservoir strain was independently associated with the presence of heart failure in the CA group (P < 0.001). LA minimum volume (cut-off ≥18 mL/m2) was a determinant of mortality in AL CA [Cox proportional hazard ratio (HR) 1.042 (1.003-1.082), P = 0.034 and Kaplan-Meier analysis, P = 0.016]. CONCLUSION: Characterizing LA myopathy has significant diagnostic and prognostic utility in CA. ATTR patients have increased atrial dyssynchrony, which may have implications for AF development. LA reservoir strain was associated with heart failure in CA, whilst LA minimum volume was a predictor of mortality in AL CA.

Left atrial shape as a marker of atrial myopathy in embolic stroke of undetermined source.

AIMS: Embolic stroke of undetermined source (ESUS) results in significant morbidity. A left atrial (LA) myopathy is implicated in a proportion of these patients. We hypothesized that LA shape varies by cause of stroke [CE (cardioembolic) vs. ESUS]. METHODS AND RESULTS: A total of 236 ischaemic stroke and atrial fibrillation (AF) patients and controls were recruited prospectively. AF was classified as paroxysmal AF (PAF) or persistent AF (PersAF). Stroke patients comprised CE stroke secondary to AF and ESUS. There were 81 AF (47 PAF, 34 PersAF), 50 ESUS, 57 CE patients [subdivided into CE with PAF (CEpaf) and CE with PersAF (CEpers)], and 48 controls. Echocardiographic parameters including LA volume, function, and shape/sphericity (3D LA sphericity and 2D-derived LA circularity, ellipticity, sphericity, and eccentricity indices) were evaluated. Increased LA volume and sphericity with LA dysfunction were present in CE, AF, and ESUS groups compared with controls. K-means cluster analysis demonstrated a spectrum of LA myopathy with controls at the lowest and CEpers and PersAF at the upper extremes, with ESUS, PAF, and CEpaf being similar and falling between these extremes. After adjusting for age, sex, and left ventricular (LV) and LA parameters, LA sphericity markers differentiated ESUS from controls (P < 0.01). CONCLUSION: Alterations in LA shape are present in ESUS, AF, and CE patients, particularly increased spherical remodelling. The novel markers of LA sphericity proposed may identify LA myopathy in ESUS patients and potentially guide management for secondary prevention.

Echocardiographic Assessment in Patients Recovered from Acute COVID-19 Illness.

Coronavirus (COVID-19) infections have spread rapidly worldwide and posed an immense public health problem. COVID-19 infection can affect the cardiovascular system both acutely and in patients followed up some period after COVID-19 infection. The aim of this study was to evaluate left ventricular (LV) and right ventricular (RV) function by echocardiography in COVID-19 recovered patients (hospitalized and non-hospitalized). Forty-two patients who recovered from COVID-19 but had ongoing symptoms were included in this retrospective observational cross-sectional study. Patients were followed-up at a median time of 112 days from confirmed COVID-19 diagnosis and a comprehensive echocardiogram was performed. COVID-19 patients were age- and sex-matched to healthy controls. Traditional TTE parameters and advanced echocardiographic parameters including two-dimensional LV global longitudinal strain (GLS) and RV free wall strain (FWS) were measured. LV volumes and LV ejection fraction were similar in COVID-19 patients and controls; however, LV GLS was significantly worse in the COVID-19 group (p = 0.002). Similarly, RV volumes and traditional RV function parameters were similar, but RV FWS (p = 0.009) and RV global strain (p = 0.015) were reduced. Alterations in LV and RV strain were observed in both hospitalized and non-hospitalized patients. In the subset of COVID-19 patients without any co-morbidities (n = 30), LV GLS remained reduced compared to controls. According to multivariate analysis, COVID-19 infection was the only independent determinant of reduced LV GLS (p = 0.012), while COVID-19 infection, diastolic blood pressure, and RV fractional area change were determinants of RV FWS. In this observational study, prior COVID-19 infection demonstrated LV dysfunction in patients with persistent symptoms. Abnormal LV strain was evident in both hospitalized and non-hospitalized patients, suggesting that these changes are independent of the severity of COVID-19 infection at presentation. The use of LV GLS in COVID-19 patients could have potential clinical utility to support the indication for cardiac magnetic resonance imaging in patients with possible COVID-19 related myocarditis. Future longitudinal studies are needed to evaluate its correlation with adverse cardiovascular events.

A novel echocardiographic risk score for light-chain amyloidosis.

Aims: The prognosis of light-chain (AL) amyloidosis, a plasma cell dyscrasia, is largely determined by the presence of cardiac involvement. Conventional staging is achieved using cardiac biomarkers (high-sensitivity troponin, N-terminal pro-beta natriuretic peptide) and free light-chain difference (Mayo staging). We sought to evaluate the role of echocardiographic parameters as prognostic markers in AL amyloidosis and examine their utility compared with conventional staging. Methods and results: Seventy-five consecutive patients with AL amyloidosis reviewed at a referral amyloid clinic who underwent comprehensive echocardiographic assessment were retrospectively identified. The evaluated echocardiographic parameters included left ventricular (LV) ejection fraction, mass, diastolic function parameters, global longitudinal strain (GLS), and left atrial (LA) volume. Mortality was assessed through a review of clinical records. During a median follow-up of 51 months, 29/75 (39%) patients died. Patients who died had a larger LA volume (47 ± 12 vs. 35 ± 10 mL/m2, P < 0.001) and a higher E/e' (18 ± 10 vs. 14 ± 6, P = 0.026). Univariate clinical and echocardiographic predictors of survival included LA volume, E/e', e', LVGLS, and Mayo stage (at significance of P < 0.1). Left atrial volume and LVGLS were significant determinants of mortality when examined using clinical cut-offs, although E/e' was not. A composite echocardiographic risk score comprising LA volume and LVGLS provided similar prognostic performance to Mayo stage [area under the curve (AUC) 0.75, 95% confidence interval (CI) 0.64-0.85 vs. AUC 0.75, 95% CI 0.65-0.858, P = 0.91]. Conclusion: Left atrial volume and LVGLS were independent predictors of mortality in AL amyloidosis. A composite echocardiographic score combining LA volume and LVGLS has similar prognostic power to Mayo stage for all-cause mortality.

Cardiac "hypertrophy" phenotyping: differentiating aetiologies with increased left ventricular wall thickness on echocardiography.

Aims: Differentiating phenotypes of cardiac "hypertrophy" characterised by increased wall thickness on echocardiography is essential for management and prognostication. Transthoracic echocardiography is the most commonly used screening test for this purpose. We sought to identify echocardiographic markers that distinguish infiltrative and storage disorders that present with increased left ventricular (LV) wall thickness, namely, cardiac amyloidosis (CA) and Anderson-Fabry disease (AFD), from hypertensive heart disease (HHT). Methods: Patients were retrospectively recruited from Westmead Hospital, Sydney, and Princess Alexandra Hospital, Brisbane. LV structural, systolic, and diastolic function parameters, as well as global (LVGLS) and segmental longitudinal strains, were assessed. Previously reported echocardiographic parameters including relative apical sparing ratio (RAS), LV ejection fraction-to-strain ratio (EFSR), mass-to-strain ratio (MSR) and amyloidosis index (AMYLI) score (relative wall thickness × E/e') were evaluated. Results: A total of 209 patients {120 CA [58 transthyretin amyloidosis (ATTR) and 62 light-chain (AL) amyloidosis], 31 AFD and 58 HHT patients; mean age 64.1 ± 13.7 years, 75% male} comprised the study cohort. Echocardiographic measurements differed across the three groups, The LV mass index was higher in both CA {median 126.6 [interquartile range (IQR) 106.4-157.9 g/m2]} and AFD [median 134 (IQR 108.8-152.2 g/m2)] vs. HHT [median 92.7 (IQR 79.6-102.3 g/m2), p < 0.05]. LVGLS was lowest in CA [median 12.29 (IQR 10.33-15.56%)] followed by AFD [median 16.92 (IQR 14.14-18.78%)] then HHT [median 18.56 (IQR 17.51-19.97%), p < 0.05]. Diastolic function measurements including average e' and E/e' were most impaired in CA and least impaired in AFD. Indexed left atrial volume was highest in CA. EFSR and MSR differentiated secondary (CA + AFD) from HHT [receiver operating curve-area under the curve (ROC-AUC) of 0.80 and 0.91, respectively]. RAS and AMYLI score differentiated CA from AFD (ROC-AUC of 0.79 and 0.80, respectively). A linear discriminant analysis with stepwise variable selection using linear combinations of LV mass index, average e', LVGLS and basal strain correctly classified 79% of all cases. Conclusion: Simple echocardiographic parameters differentiate between different "hypertrophic" cardiac phenotypes. These have potential utility as a screening tool to guide further confirmatory testing.