Degradation of Perfluorododecyl-Iodide Self-Assembled Monolayers upon Exposure to Ambient Light.

Perfluorododecyl iodide (I-PFC12) is of interest for area-selective deposition (ASD) applications as it exhibits intriguing properties such as ultralow surface energy, the ability to modify silicon's band gap, low surface friction, and suitability for micro-contact patterning. Traditional photolithography is struggling to reach the required critical dimensions. This study investigates the potential of using I-PFC12 as a way to produce contrast between the growth area and non-growth areas of a surface subsequent to extreme ultraviolet (EUV) exposure. Once exposed to EUV, the I-PFC12 molecule should degrade with the help of the photocatalytic substrate, allowing for the subsequent selective deposition of the hard mask. The stability of a vapor-deposited I-PFC12 self-assembled monolayer (SAM) was examined when exposed to ambient light for extended periods of time by using X-ray photoelectron spectroscopy (XPS). Two substrates, SiO2 and TiO2, are investigated to ascertain the suitability of using TiO2 as a photocatalytic active substrate. Following one month of exposure to light, the atomic concentrations showed a more substantial fluorine loss of 10.2% on the TiO2 in comparison to a 6.2% loss on the SiO2 substrate. This more pronounced defluorination seen on the TiO2 is attributed to its photocatalytic nature. Interestingly, different routes to degradation were observed for each substrate. Reference samples preserved in dark conditions with no light exposure for up to three months show little degradation on the SiO2 substrate, while no change is observed on the TiO2 substrate. The results reveal that the I-PFC12 SAM is an ideal candidate for resistless EUV lithography.

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%.

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.

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.

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.

Area-Selective Deposition of AlOx and Al-Silicate for Fully Self-Aligned Via Integration.

The rush for better-performing electronics, and manufacturing processes that heavily rely on "top-down" patterning techniques, is making the integration of "self-aligned" fabrication methods, such as area-selective deposition (ASD), a critical objective for continued device scaling. The fully self-aligned via (FSAV) scheme is broadly proposed as a "killer application" to determine whether ASD can shift from an R&D process to high-volume manufacturing. Nevertheless, the lack of a suitable low-κ deposition process has prevented the realization of FSAV by dielectric-on-dielectric ASD. This is primarily due to the high temperature and/or strong oxidizers employed during low-κ dielectric deposition and their unsuitability in the presence of organic masks, such as self-assembled monolayers (SAMs), used to prevent material nucleation during ASD. In this work, AlOx and Al-silicate atomic layer deposition (ALD) processes are studied to provide suitable materials for ASD-enabled FSAV. Dimethylaluminum isopropoxide and H2O are utilized to deposit the metal oxide, whereas Al-silicate is grown by adding 2,2-dimethoxy-1,6-diaza-2-silacyclooctane (DMDAcO) pulses to the AlOx ALD cycle. The selectivity of such processes is demonstrated on 50 nm Cu/SiO2 structures, using octadecanethiol-derived SAMs to inhibit material nucleation on the metal lines. Scanning and transmission electron microscopies are employed to assess the quality of the ASD processes and investigate the mechanisms behind defect generation on a nongrowth surface. X-ray photoelectron spectroscopy measurements show the high purity of the AlOx film, whereas DMDAcO-ligand incorporation into the Al-silicate matrix is observed. Planar capacitor structures are used to assess the electrical properties of both ASD films, revealing that the silicate film exhibits a relatively low κ-value (5.3 ± 0.2), with a high acceleration field factor (32.4 ± 1.4) and a dielectric breakdown voltage of 6.0 ± 0.3 V at 100 °C.

Investigating the Efficacy of Hafnium Dioxide Barrier Layers to Halt Copper Oxide Formation in Redistribution Layers for Three-Dimensional (3D) Packaging.

HfO2 is investigated for its suitability to act as an oxygen and moisture barrier to prevent Cu oxidation in redistribution layers (RDLs) in 3D packaging technologies. HfO2 barriers of varying thicknesses were deposited via atomic layer deposition (ALD) on Cu surfaces and then stressed by (i) high temperature stress and (ii) humidity and thermal stress for 1000 h to ascertain the optimal thickness to prevent oxidation of the Cu. The thickness of the ALD HfO2 film was monitored by ellipsometry, while the extent of Cu oxidation was monitored by focus ion beam prepared SEM cross sections. It is found that ∼9 nm of HfO2 is sufficient to prevent Cu oxidation.

Alterations in multi-layer strain in AL amyloidosis.

BACKGROUND: Cardiac involvement in AL amyloidosis portends a poor prognosis. 2D-speckle tracking echocardiography (2D-STE) strain can identify subclinical cardiac involvement. This study performed multilayer and multiplanar 2D-STE myocardial strain analysis. METHODS: We compared 75 AL amyloidosis patients to 49 hypertensive patients and 49 healthy controls. Longitudinal strain was obtained from epicardial, mid-myocardial and endocardial layers; segmental strain was measured from mid-myocardial basal, mid and apical segments. RESULTS: Global longitudinal strain was reduced in epicardial (-14.3 ± -4.0% vs. -17.4 ± 2.2% vs. -17.5 ± -2.0%, p < .001), mid-myocardial (-16.3 ± -4.5% vs. -19.7 ± 2.5% vs. -19.7 ± -2.2%, p < .001) and endocardial layers (-18.7 ± -4.9% vs. -22.2 ± 3.0% vs. -22.3 ± -2.6%, p < .001) in amyloid patients compared to hypertensive and healthy controls. Segmental strain confirmed significant reduction in basal (-11.2 ± -3.9% vs. -17.6 ± 2.7% vs. -20.9 ± -3.4%, p < .001) and mid (-14.8 ± -4.3% vs. -19.2 ± 2.5% vs. -19.6 ± -2.2%, p < .001) LV segments in the AL amyloid group. Receiver operating curve analysis demonstrated that an optimal cut-off of -16% for basal segmental strain better differentiated AL amyloid from hypertensive group (sensitivity 96%, specificity 70%, AUC 0.93), compared to relative apical sparing (AUC of 0.85). CONCLUSION: Strain demonstrated myocardial involvement in all layers in AL amyloidosis, with reduced basal segmental longitudinal strain a likely marker of early disease.

Electrocardiographic Characteristics and Their Correlation with Echocardiographic Alterations in Fabry Disease.

Fabry disease (FD) is an X-linked disorder with α-galactosidase A deficiency. Males (>30 years) and females (>40 years) often present with cardiac manifestations, predominantly left ventricular hypertrophy (LVH). The aim of this study was to evaluate electrocardiographic (ECG) characteristics within FD patients to identify gender related differences, and to additionally explore the association of ECG parameters with structural and functional alterations on transthoracic echocardiography (TTE). Retrospective cross-sectional analysis of 45 FD patients with contemporaneous ECG and TTE was performed and compared to age and gender matched healthy controls. FD patients demonstrated alterations in several ECG parameters particularly in males, including prolonged P-wave duration (91 vs. 81 ms, p = 0.022), prolonged QRS duration (96 vs. 84 ms, p < 0.001), increased R-wave amplitude in lead I (8.1 vs. 5.7 mV, p = 0.047), increased Sokolow-Lyon index (25 vs. 19 mV, p = 0.002) and were more likely to meet LVH criteria (31% vs. 7%, p = 0.006). FD patients with impaired basal longitudinal strain (LS) on TTE were more likely to meet LVH criteria (41% vs. 0%, p = 0.018). Those with more advanced FD (increased LV wall thickness on TTE) were more likely to meet LVH criteria but additionally demonstrated prolonged ventricular depolarization (QRS duration 101 vs. 88 ms, p = 0.044). Therefore, alterations on ECG demonstrating delayed atrial activation, delayed ventricular depolarization and evidence of LVH were more often seen in male FD patients. Impaired basal LS, a TTE marker of early cardiac involvement, correlated with ECG abnormalities. Increased LV wall thickness on TTE, a marker of more advanced FD, was associated with more severe ECG abnormalities.

Basal Segmental Longitudinal Strain: A Marker of Subclinical Myocardial Involvement in Anderson-Fabry Disease.

BACKGROUND: Cardiac involvement in Anderson-Fabry disease (AFD) is associated with increased left ventricular (LV) wall thickness. The aim of this study was to evaluate if two-dimensional global and regional strain in patients with AFD can identify early myocardial involvement (when LV wall thickness and function are normal). Additionally, the association of altered strain with adverse cardiovascular events was evaluated. METHODS: In a retrospective cross-sectional study, 43 patients with AFD, before enzyme replacement therapy (mean age, 44 ± 12 years; 58.1% men), were compared with age- and gender-matched healthy control subjects. The mean follow-up duration among patients with AFD for major adverse cardiovascular events (MACE) was 82 months. RESULTS: LV ejection fraction was similar between groups (patients with AFD vs control subjects, 61 ± 8% vs 61 ± 6%; P = .89). However, global longitudinal strain (LS) was impaired in patients with AFD compared with control subjects (-16.5 ± 3.8% vs -20.2 ± 1.7%, P < .001), with greater impairment in patients with AFD with increased LV wall thickness (-15.4 ± 3.9% vs -18.7 ± 2.3%, P < .006). Additionally, LS was most impaired in the basal segments in patients with AFD (-14.8 ± 3.7% vs -20.3 ± 1.1%, P < .001). MACE occurred in 19 of 43 patients (four women, 15 men), and Kaplan-Meier analysis demonstrated that MACE were associated with impaired basal LS. CONCLUSIONS: In patients with AFD, altered basal LS is present even in those with normal LV wall thickness and is associated with MACE. Therefore, basal LS should be considered when screening for cardiac involvement in AFD, particularly in female patients with AFD with normal LV wall thickness.

H2O2-assisted photoelectrocatalytic degradation of Mitoxantrone using CuO nanostructured films: Identification of by-products and toxicity.

CuO nanostructured thin films supported on silicon with 6.5 cm2 area (geometric area greater than the studies reported in the literature) were synthesized by a chemical bath deposition technique. The electrodes were characterized by MEV, XRD, XPS, contact angle, cyclic voltammetry and electrochemical impedance spectroscopy analyses. To evaluate the photoelectrochemical properties of the CuO films, photocurrent-voltage measurements were performed using linear voltammetry. The catalytic activities of CuO nanostructures were evaluated by monitoring photodegradation of Mitoxantrone (MTX) under UV-A light irradiation. The method of photoelectrocatalysis (PEC), applying a voltage of 1.5 V and assisted by adding H2O2, was undertaken. To the best of our knowledge, no studies on the degradation of anticancer agents using PEC process have been found in the literature. For comparison purposes, experiments were performed under the same conditions by assisted photocatalysis (PC) with H2O2 and direct photolysis. CuO deposits consist of a needle-like morphology. The presence of CuO in the tenorite phase was evidenced by XRD and the XPS spectra showed the presence of copper(II) oxide. The increase in current under illumination shows that CuO exhibits photoactivity. The PEC system showed a 75% level of MTX degradation, while the level achieved using PC was 50%. Under UV-A light alone only 3% removal was obtained after 180 min. Up to 10 by-products were identified by chromatography-mass spectrometry (LC-MS) with m/z values ranging between 521 and 285 and a plausible degradation route has been proposed. It is worth mentioning that 9 by-products identified in this work, were not found in the literature in other studies of degradation or products generated as metabolites. The toxicity tests of MTX before and after PEC treatment with Artemia Salina and Allium cepa showed a decrease in the acute toxicity of the medium as the antineoplastic was degraded.

Left atrial function: evaluation by strain analysis.

The left atrium has an important role in modulating left ventricular filling and is an important biomarker of cardiovascular disease and adverse cardiovascular outcomes. While previously left atrial (LA) size was utilised, the role of LA function as a biomarker is increasingly being evaluated, both independently and also in combination with LA size. Strain analysis has been utilised for evaluation of LA function and can be measured throughout the cardiac cycle, thereby enabling the evaluation of LA reservoir, conduit and contractile function. Strain evaluates myocardial deformation while strain rate examines the rate of change in strain. This review will focus on the various types of strain analysis for evaluation of LA function, alterations in LA strain in physiological and pathologic states that alter LA function and finally evaluate its utility as a prognostic marker.

Anthracyclines induce early changes in left ventricular systolic and diastolic function: A single centre study.

AIMS: 2 dimensional (2D) strain analysis detects subclinical left ventricular (LV) systolic dysfunction. Our aim was to evaluate changes in LV systolic and diastolic function in breast cancer patients early after anthracycline chemotherapy, and to identify predisposing factors. METHODS AND RESULTS: 140 patients were assessed by detailed echocardiography before and within seven days post treatment. LV ejection fraction (LVEF), global longitudinal strain (GLS), strain rate and radial and circumferential strain were assessed. Additionally, left atrial volumes and LV diastolic parameters were evaluated. LVEF although reduced after treatment, remained within the normal range (60±3% vs. 59±3%, p = 0.04). Triplane GLS was significantly reduced after treatment (-20.0±1.6% vs. -19.1±1.8%, p<0.001). Subclinical LV dysfunction (>11% reduction in GLS compared to before therapy) occurred in 22% (29/135). Impaired diastolic function grade significantly increased from 46% to 57% (p<0.001) after treatment. Furthermore, diastolic dysfunction was more common in the subgroup group with reduced systolic GLS compared to those without changes in GLS (30% vs. 11%; p = 0.04). No risk factors or clinical parameters were associated with the development of subclinical LV dysfunction; however the percentage change in early diastolic strain rate and the E velocity were independent predictors of >11% reduction in GLS. CONCLUSION: Twenty two percent of patients had subclinical LV dysfunction by GLS, whilst none had cardiotoxicity defined by LVEF, demonstrating that GLS is more sensitive for detection of subclinical LV systolic dysfunction immediately after anthracycline therapy. Diastolic dysfunction increased, particularly in the group with reduced GLS, demonstrating the close pathophysiological relationship between systolic and diastolic function.

Independent Echocardiographic Markers of Cardiovascular Involvement in Chronic Kidney Disease: The Value of Left Atrial Function and Volume.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular mortality and morbidity, particularly ischemic heart disease and cardiomyopathy. Newer echocardiographic techniques such as myocardial strain analysis provides the opportunity to detect early myocardial dysfunction. The aim of this study was to examine echocardiographic parameters, in particular left atrial (LA) function and volume, in patients with CKD. A further aim was to determine echocardiographic parameters that are sensitive to detect cardiovascular involvement in early CKD. METHODS: Seventy-six patients with stage 3 CKD (estimated glomerular filtration rate, 30-59 mL/min/1.73 m(2)) with hypertension and/or diabetes mellitus, without any previous cardiac illness, were prospectively recruited. These patients were compared with subjects matched for age, sex, and risk factors (hypertension and/or diabetes mellitus) with normal renal function and 76 healthy age-matched control subjects. Two-dimensional strain analyses of the left atrium and left ventricle were performed. Comprehensive echocardiographic examinations were performed in all participants, and traditional echocardiographic parameters including indexed LA volume (LAVI) and two-dimensional strain analysis of the left ventricle and left atrium were performed in all participants. Differences among the three groups on demographic, clinical, and echocardiographic parameters were examined. RESULTS: LA systolic strain (20.9 ± 6.3% vs 27.4 ± 7.9%, P < .0001) and systolic and late diastolic strain rates were altered in the CKD group, while early diastolic strain rate was similar to that in the risk factor-matched group. LAVI was significantly larger in the CKD group compared with the risk factor-matched group and healthy control subjects (38.5 ± 10 vs 31.2 ± 9 vs 22.3 ± 5 mL/m(2), P < .0001). LV strain as well as LV systolic and early diastolic strain rates were similar in the CKD and risk factor-matched groups. LV late diastolic strain rate, a surrogate measure of LA contractile function, was, however, reduced in the CKD group. Forward logistic regression analysis showed LA global strain to be the most sensitive predictor for the presence of CKD, followed by LAVI; though LV late diastolic strain rate was reduced in the CKD group, it was not an independent predictor. Furthermore, the addition of LA strain to traditional echocardiographic parameters significantly increased the predictive power to detect cardiovascular involvement (C statistic = 0.65 vs C statistic = 0.84, P < .0001). Increased LAVI, reduced left ventricular global strain, and the presence of CKD were independent predictors of LA strain, while left ventricular mass index, E/e' ratio, and the presence of CKD were predictors of LAVI. CONCLUSION: LA strain and LAVI are more sensitive parameters than traditional echocardiographic parameters as well as left ventricular strain in patients with early CKD. LA strain and LAVI may be useful to detect myocardial involvement in stage 3 CKD, and LA alterations may be consequent to increased activation of the renin-angiotensin-aldosterone pathway, causing myocardial fibrosis in CKD.

Principles of transthoracic echocardiographic evaluation.

Transthoracic echocardiography is the most widely used imaging test in cardiology. Although completely noninvasive, transthoracic echocardiography has a well-established role in the diagnosis of numerous cardiovascular diseases, and also provides critical qualitative and quantitative information on their prognosis and pathophysiological processes. The aim of this Review is to outline the broad principles of transthoracic echocardiography, including the traditional techniques of two-dimensional, colour, and spectral Doppler echocardiography, and newly developed advances including tissue Doppler, myocardial deformation imaging, torsion, stress echocardiography, contrast and three-dimensional echocardiography. The advantages and disadvantages, clinical application, prognostic value, and salient research findings of each modality are described. Advances in complex imaging techniques are expected to continue unabated, and this Review highlights technical improvements that will influence the diagnosis and improve our understanding of cardiovascular function and disease.

Effects of age and gender on right ventricular systolic and diastolic function using two-dimensional speckle-tracking strain.

BACKGROUND: Accurate assessment of the right ventricle is increasingly important. Measures of right ventricular (RV) systolic function, including fractional area change, tissue Doppler (s' velocity), and tricuspid annular plane systolic excursion, show significant variation, and the impacts of age and gender are unclear. The aim of this study was to determine the effects of gender and age on global and segmental RV systolic and diastolic function using both traditional echocardiographic and two-dimensional strain parameters. METHODS: Detailed transthoracic echocardiographic studies were performed on 142 healthy adult volunteers, with particular emphasis on the right ventricle to determine RV dimensions and function, including fractional area change, tricuspid annular plane systolic excursion, s' velocity, global and segmental systolic strain, and systolic, early diastolic, and late diastolic strain rates. RESULTS: Tricuspid annular plane systolic excursion (r = -0.4, P < .001) and RV s' velocity (r = -0.5, P < .001) as well as diastolic functional parameters, including transtricuspid peak E velocity and RV free wall e' velocity (r = -0.4, P < .001), decreased with age. Global systolic strain was also reduced, with differential reductions in basal and mid segmental strain with age. Early diastolic strain rate decreased, with a corresponding increase in late diastolic strain rate. RV function parameters, including fractional area change, e' velocity, strain, and strain rate, were significantly lower in men. CONCLUSIONS: RV functional analysis by two-dimensional strain demonstrates a small yet significant change in global and segmental RV function with age and gender, and therefore adjustment for these measures is required in the evaluation of RV function.

Left atrial volumes: two-dimensional, three-dimensional, cardiac magnetic resonance and computed tomography measurements.

PURPOSE OF REVIEW: Evaluation of left atrial volume is important, as it is a biomarker of cardiovascular disease and outcomes and correlates with diastolic dysfunction severity. Left atrial volume measurements by different imaging modalities, including 2D and 3D echocardiography (2DE and 3DE), cardiac magnetic resonance (CMR) and computed tomography (CT), are reviewed in regard to recent advances, methodology, prognostic value and limitations. RECENT FINDINGS: Left atrial volume assessments correlate well between the different imaging modalities; however, 2DE significantly underestimates left atrial measurements. Assessment of the left atrial minimum volume and left atrial phasic function derived volumetrically have reported superior predictive value for major adverse cardiovascular events and elevated left ventricular diastolic pressure compared with the left atrial maximum volume. SUMMARY: The different imaging modalities used to assess left atrial volumes are not interchangeable, particularly for serial measurements. Although 2DE underestimates left atrial volumes, most normative as well as predictive data have been obtained using this modality. Standardization, with established normative data and classification criteria, needs to be established for other imaging modalities, additionally incorporating assessment of left atrial minimum and phasic volumes. Despite the limitations of the more simplistic 2DE, its measurements are well defined with significant prognostic value. The incremental prognostic value of the more complex imaging techniques needs to be further validated.

Chronic kidney disease is independently associated with alterations in left atrial function.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality; hence detection of early cardiovascular involvement in CKD is important to prevent future adverse cardiovascular events. Left atrial (LA) enlargement and dysfunction has been reported in end stage renal disease. However, there is a paucity of published data regarding the evaluation of LA function in CKD using noninvasive imaging parameters. In this study, we evaluated biplane LA volume as well as LA function (LA global systolic strain (GS) and strain rate [SR]) in stage 3 CKD patients (eGFR 30-59 mL/min per 1.73 m(2) ) to determine if LA function parameters are more significantly altered by the presence of CKD in addition to changes due to hypertension alone. METHODS: Thirty-three CKD patients (eGFR 30-59 mL/min per 1.73 m(2) ) with hypertension were compared to 33 normal controls and 34 hypertensive (HT) subjects with normal renal function; all participants underwent a detailed transthoracic echocardiogram. Indexed biplane LA volume (LAVI), LA segmental function, and GS and SR (systolic, early, and late diastole) derived from tissue Doppler imaging (TDI) were measured. Univariate predictors of LA strain were determined. Multiple logistic regression analysis was used to examine the effect of patient group (i.e. CKD) on GS and SR as well as LAVI. RESULTS: Left atrial volume indexed was significantly increased in both the HT and CKD with HT group compared to normal controls (28 ± 9 mL/m(2) vs. 28 ± 9 mL/m(2) vs. 23 ± 5 mL/m(2) , respectively, P = 0.02). However, LAVI was similar in the HT and CKD with HT group (28 ± 9 mL/m(2) vs. 28 ± 9 mL/m(2) ; P = NS). LA GS and SR were reduced in both the CKD with HT and HT group, compared to controls. However, a significantly lower LA GS was present in the CKD with HT group (Controls vs. HT vs. CKD with HT: 54.9 ± 14.5% vs. 34.5 ± 6.2% vs. 25.7 ± 9.3%, respectively; P = 0.001). To examine the effect of group, (i.e. presence of CKD) multiple logistic regression analysis was performed with univariate predictors including indexed left ventricular mass (LVMI), LV diastolic grade, LAVI, peak A-wave velocity, ß-blocker therapy, GS and SR; this demonstrated that CKD had an independent effect on LA GS and SR (systolic, early, and late diastole). GS demonstrated moderate correlation with systolic blood pressure (r = -0.5, P = 0.01), diastolic grade (r = -0.5, P = 0.01), E' velocity (r = 0.6, P = 0.0001), peak A velocity (r = -0.5, P = 0.004), and LAVI (r = -0.6, P = 0.002). CONCLUSIONS: Left atrial dysfunction is evident in stage 3 CKD with associated LA enlargement. This study demonstrates that LA GS and SR were reduced in the CKD group despite similar LAVI in the CKD with HT and HT group. Hence LA GS and SR may be a more sensitive noninvasive tool to detect cardiovascular involvement in CKD.

Left atrial enlargement and reduced atrial compliance occurs early in Fabry cardiomyopathy.

BACKGROUND: Fabry disease is associated with left ventricular hypertrophy (LVH) and myocardial fibrosis. The aim of this study was to evaluate left atrial (LA) size and function using tissue Doppler-derived strain in patients with Fabry disease. METHODS: Echocardiography was performed in 33 Fabry patients (14 without LVH, 19 with LVH) before commencement of enzyme replacement therapy, and results were compared with those from age-matched and gender-matched controls (n=28 and n=38, respectively). Atrial strain and strain rate were measured from four segments in the apical four-chamber and two-chamber views of the LA, and global values were calculated. Systolic strain, systolic strain rate, early diastolic strain rate, and late diastolic strain rate were measured. Phasic LA volumes and fractions were calculated. Mitral inflow and tissue Doppler E' velocities were used to estimate left ventricular (LV) diastolic function. RESULTS: LA volume was increased in Fabry patients, even in the absence of LVH. Importantly, diastolic function was normal in this subgroup without LVH, with E' velocities similar to those in controls. LA systolic strain and early diastolic strain rate were selectively reduced in Fabry patients with LVH and reflect reductions in LA and LV relaxation, respectively, consequent to increased LV mass. However, independent of LVH, both Fabry groups had significant reductions in systolic strain rate and increased LA stiffness index. CONCLUSIONS: Fabry disease is associated with LA enlargement and reduced atrial compliance that occurs before the development of LVH. This suggests that Fabry cardiomyopathy may not only cause ventricular hypertrophy and fibrosis but also alters atrial myocardial properties early in the disease process. Consequently, measurements of LA size and function may be useful in the early diagnosis of Fabry disease, before the development of LVH.