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.

Segmental Cardiac Radiation Dose Determines Magnitude of Regional Cardiac Dysfunction.

Background Subclinical left ventricular dysfunction detected by 2-dimensional global longitudinal strain post breast radiotherapy has been described in patients with breast cancer. We hypothesized that left ventricular dysfunction postradiotherapy may be site specific, based on differential segmental radiotherapy dose received. Methods and Results Transthoracic echocardiograms were performed at baseline, 6 weeks, and 12 months postradiotherapy on 61 chemotherapy-naïve women with left-sided breast cancer undergoing tangential breast radiotherapy. Radiation received within basal, mid, and apical regions for the 6 left ventricular walls was quantified from the radiotherapy treatment planning system. Anterior, anteroseptal, and anterolateral walls received the highest radiation doses, while inferolateral and inferior walls received the lowest. There was a progressive increase in the radiation dose received from basal to apical regions. At 6 weeks, the most significant percentage deterioration in strain was seen in the apical region, with greatest reductions in the anterior wall followed by the anteroseptal and anterolateral walls, with a similar pattern persisting at 12 months. There was a within-patient dose-response association between the segment-specific percentage deterioration in strain at 6 weeks and 12 months and the radiation dose received. Conclusions Radiotherapy for left-sided breast cancer causes differential segmental dysfunction, with myocardial segments that receive the highest radiation dose demonstrating greatest strain impairment. Percentage deterioration in strain observed 6 weeks postradiotherapy persisted at 12 months and demonstrated a dose-response relationship with radiotherapy dose received. Radiotherapy-induced subclinical cardiac dysfunction is of importance because it could be additive to chemotherapy-related cardiotoxicity in patients with breast cancer. Long-term outcomes in patients with asymptomatic strain reduction require further investigation.

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.

Persistent reduction in global longitudinal strain in the longer term after radiation therapy in patients with breast cancer.

BACKGROUND: More than 80% of breast cancer patients receive radiotherapy (RT). However, RT can lead to cardiotoxicity, which usually develops insidiously over years, making diagnosis difficult. It is also unknown whether early identification of at-risk patients might improve long-term outcome. We have previously described subclinical alterations, detected by two-dimensional speckle tracking strain echocardiography, in left ventricular (LV) function immediately following RT in breast cancer. HYPOTHESIS: Subclinical myocardial alterations in LV function consequent to RT cardiotoxicity, observed early, persist at 12 months. METHODS: 40 chemotherapy naive women with left-sided breast cancer, treated with surgery and adjuvant breast RT, were prospectively recruited from two tertiary hospitals. Transthoracic echocardiography was performed at baseline (pre-RT), 6 weeks post-RT, and 12 months post-RT. RESULTS: An increase in LV end diastolic and end systolic volumes was seen from baseline, consistent with persistent LV remodelling; however, due to the increase in both systolic and diastolic volumes over time, no change in LV ejection fraction (EF) was observed. Global longitudinal strain (GLS) and S' velocity remained significantly lower at 12 months post-RT. GLS dropped by >10% in 16 patients and by >20% in 4 patients compared to baseline. CONCLUSIONS: Subclinical cardiac dysfunction using strain analysis, evident early, persists one year after RT, despite unchanged conventional indices such as LVEF. Persistent GLS reduction may be of particular importance in breast cancer patients receiving concomitant chemotherapy. Longer term prospective studies are required to determine if reductions in strain post-RT are associated with future adverse cardiovascular events.

Strain Imaging Detects Dose-Dependent Segmental Cardiac Dysfunction in the Acute Phase After Breast Irradiation.

PURPOSE: We examined the utility of echocardiographic 2-dimensional speckle tracking strain imaging (SI) for the evaluation of segmental myocardial dysfunction before and after radiation therapy (RT) and the relationship to dose exposure. METHODS AND MATERIALS: We prospectively recruited 40 women with left-sided breast cancer, undergoing only adjuvant RT to the left chest. Comparisons of traditional echocardiographic parameters and SI parameters at baseline and 6 weeks after RT were analyzed. Regional strain and strain rate (SR) parameters were obtained from all 18 left ventricular segments. The correlation of change in strain parameters with segmental radiation dose was examined. RESULTS: We observed a significant reduction in global and segmental systolic strain parameters at 6 weeks after RT compared with baseline, with the largest decrement in the apical segments; this corresponded with the segments receiving the highest radiation dose exposure (apical peak systolic strain of -21.21% ± 3.49% before RT vs -18.69% ± 3.34% after RT, percentage change of 11.88%, P=.002; apical peak systolic SR of -1.17 ± 0.24 s-1 before RT vs -1.04 ± 0.19 s-1 after RT, percentage change of 11.11%, P=.008). There was a modest correlation between the apical segment systolic strain reduction and radiation dose exposure (apical segment Δ change and apical radiation dose, r=0.345, P=.031; apical segment percentage change and apical radiation dose, r=0.346, P=.031). A significant reduction in early diastolic SR was observed in the apical segments after treatment compared with baseline (apical early diastolic SR, 1.54 ± 0.45 s-1 before RT vs 1.35 ± 0.33 after RT s-1; percentage change, 12.34%; P=.034). CONCLUSIONS: Two-dimensional SI detected dose-related regional myocardial dysfunction in the acute phase after RT in chemotherapy-naive left-sided breast cancer patients. Although the long-term effects remain unknown, this imaging modality may have a potential role in the evaluation of irradiation-related cardiotoxicity.

Evaluation of traditional and novel echocardiographic methods of cardiac diastolic dysfunction post radiotherapy in breast cancer.

BACKGROUND: To investigate alterations in left ventricular (LV) diastolic function using traditional and novel echocardiographic parameters, following radiation therapy (RT) in breast cancer patients in the acute setting. METHODS: 40 chemotherapy-naïve women with left-sided breast cancer undergoing RT were prospectively recruited. A comprehensive transthoracic echocardiogram (TTE) was performed at baseline, during RT and 6weeks post-RT. Traditional echocardiographic diastolic parameters and diastolic strain rate were measured and analysed. The relationship between alterations in diastolic parameters, changes in global longitudinal systolic strain (GLS) and radiation dose were investigated. RESULTS: Traditional diastolic parameters remained largely unchanged; however diastolic strain parameters, E-Sr and A-Sr were significantly reduced 6weeks post-RT [Longitudinal E-Sr (s-1) 1.47+/-0.32 vs 1.29+/-0.27*; Longitudinal A-Sr (s-1) 1.19+/-0.31 vs 1.03+/-0.24*; *p<0.05 vs baseline]. When patients were divided by a reduction ≥10% versus <10% in GLS post-RT, a greater reduction in both traditional diastolic and diastolic strain parameters was observed in the group with >10% reduction in systolic function as evaluated by GLS. When patients were divided by mean v30 dose, a greater % change in E-Sr was noted in those receiving more than mean V30 dose. CONCLUSION: Diastolic dysfunction was only evident acutely, post-RT with the use of newer methods like strain analysis. A significant reduction in diastolic function was seen in the patient subgroup with ≥10% reduction in systolic function, enhancing the notion of diastolic function as a potential indicator for systolic dysfunction. Future longitudinal studies are required to determine the specific prognostic value of these observations.

Come Clean for Surgery.

When patients are brought to the operating theatre a series of checks are performed to reduce harm or potential harm to our patients. One harm that can cause significant morbidity and mortality to our patients is surgical site infection (SSI). Reducing SSIs requires a multi-faceted approach prior to the incision. Prophylactic antibiotics are given, if indicated, along with glucose and temperature control as part of an SSI bundle. Meticulous attention is paid by the team to ensure that the surgical field is prepared with antiseptic solutions such as chlorhexidine or betadine. The airflow changes in theatres also help minimise the risk of infection. The surgeon and scrub team are trained to undertake strict asepsis when 'scrubbing up'. The rest of the team are careful to ensure hand hygiene and appropriate glove use at all times.

Alterations in regional myocardial deformation assessed by strain imaging in cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis results in increased left ventricular (LV) wall thickness and diastolic dysfunction (DD). Strain measurements using velocity vector imaging (VVI) may further characterize myocardial dysfunction. METHODS: A total of 43 AL amyloidosis patients were compared to age-matched normals and hypertensive patients (HT). Subgroup analysis within the amyloid group was performed based on LV wall thickness (≤14 mm, >14 mm) and diastolic dysfunction (DD) (Group 1: normal and impaired relaxation, Group 2: pseudonormal, Group 3: restrictive). LV strain (longitudinal, circumferential, and radial strain (S) and strain rate [Sr]) were measured using velocity vector imaging (VVI). RESULTS: Increased LV wall thickness and DD were observed in the amyloid group. Global longitudinal (-13.9±4.1% vs -16.7±3.8%; P=.002) and radial (27.4±13.4% vs 38.8±15.7%; P<.001) strain were lower in the amyloid group vs normal controls, while circumferential strain was similar. Segmental analysis demonstrated reduced mid- and basal segmental strain with relative sparing of apical segments in the amyloid group. Reduced longitudinal and radial strain, with preserved circumferential strain, were observed in patients with wall thickness >14 mm; however, circumferential strain was also altered when severe DD (restrictive filling) was present. CONCLUSION: Reduction in longitudinal and radial S and Sr was evident using VVI strain analysis in amyloidosis, with segmental heterogeneity in longitudinal S. There was relative preservation of circumferential strain, which was reduced only in patients with severe DD.

Subclinical cardiac dysfunction detected by strain imaging during breast irradiation with persistent changes 6 weeks after treatment.

PURPOSE: To evaluate 2-dimensional strain imaging (SI) for the detection of subclinical myocardial dysfunction during and after radiation therapy (RT). METHODS AND MATERIALS: Forty women with left-sided breast cancer, undergoing only adjuvant RT to the left chest, were prospectively recruited. Standard echocardiography and SI were performed at baseline, during RT, and 6 weeks after RT. Strain (S) and strain rate (Sr) parameters were measured in the longitudinal, circumferential, and radial planes. Correlation of change in global longitudinal strain (GLS % and Δ change) and the volume of heart receiving 30 Gy (V30) and mean heart dose (MHD) were examined. RESULTS: Left ventricular ejection fraction was unchanged; however, longitudinal systolic S and Sr and radial S were significantly reduced during RT and remained reduced at 6 weeks after treatment [longitudinal S (%) -20.44 ± 2.66 baseline vs -18.60 ± 2.70* during RT vs -18.34 ± 2.86* at 6 weeks after RT; longitudinal Sr (s(-1)) -1.19 ± 0.21 vs -1.06 ± 0.18* vs -1.06 ± 0.16*; radial S (%) 56.66 ± 18.57 vs 46.93 ± 14.56* vs 49.22 ± 15.81*; *P<.05 vs baseline]. Diastolic Sr were only reduced 6 weeks after RT [longitudinal E Sr (s(-1)) 1.47 ± 0.32 vs 1.29 ± 0.27*; longitudinal A Sr (s(-1)) 1.19 ± 0.31 vs 1.03 ± 0.24*; *P<.05 vs baseline], whereas circumferential strain was preserved throughout. A modest correlation between S and Sr and V30 and MHD was observed (GLS Δ change and V30 ρ = 0.314, P=.05; GLS % change and V30 ρ = 0.288, P=.076; GLS Δ change and MHD ρ = 0.348, P=.03; GLS % change and MHD ρ = 0.346, P=.031). CONCLUSIONS: Subclinical myocardial dysfunction was detected by 2-dimensional SI during RT, with changes persisting 6 weeks after treatment, though long-term effects remain unknown. Additionally, a modest correlation between strain reduction and radiation dose was observed.

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.

Safety and efficacy of rescue angioplasty for ST-elevation myocardial infarction with high utilization rates of glycoprotein IIb/IIIa inhibitors.

BACKGROUND: Fibrinolytic therapies remain widely used for ST-elevation myocardial infarction, and for "failed reperfusion," rescue percutaneous coronary intervention (PCI) is guideline recommended to improve outcomes. However, these recommendations are based on data from an earlier era of pharmacotherapy and procedural techniques. METHODS AND RESULTS: To determine factors affecting prognosis after rescue PCI, we studied 241 consecutive patients (median age 55 years, interquartile range [IQR] 48-65) undergoing procedures between 2001 and 2009 (53% anterior ST-elevation myocardial infarction and 78% transferred). The median treatment-related times were 1.2 hours (IQR 0.8-2.2) from symptom onset to door, 2 hours (IQR 1.3-3.2) from symptom onset to fibrinolysis (93% tenecteplase), and 3.9 hours (IQR 3.1-5.2) from fibrinolysis to balloon. Procedural characteristics were stent deployment in 95% (11.6% drug eluting) and 78% glycoprotein IIb/IIIa inhibitor use, and Thrombolysis In Myocardial Infarction (TIMI) 3 flow rates pre-PCI and post-PCI were 41% and 91%, respectively (P < .001). At 30 days, TIMI major bleeding occurred in 16 (6.6%) patients, and 23 (9.5%) patients received transfusions; nonfatal stroke occurred in 4 (1.7%) patients (2 hemorrhagic). Predictors of TIMI major bleeding were female gender (odds ratio 3.194, 95% CI 1.063-9.597; P = .039) and pre-PCI shock (odds ratio 3.619, 95% CI,1.073-12.207; P = .038). Mortality at 30 days was 6.2%, and 3.2% in patients without pre-PCI shock. One-year mortality was 8.2% (5.3% in patients without pre-PCI cardiogenic shock), 5.2% had reinfarction, and the target vessel revascularization rate was 6.4% (2.6% in arteries ≥ 3.5 mm in diameter). Pre-PCI shock, female gender, and post-PCI TIMI flow grades ≤ 2 were significant predictors of 1-year mortality on multivariable regression modeling, but TIMI major bleeding was not. CONCLUSIONS: Rescue PCI with contemporary treatments can achieve mortality rates similar to rates for contemporary primary PCI in patients without pre-PCI shock. Whether rates of bleeding can be reduced by different pharmacotherapies and interventional techniques needs clarification in future studies.

Echocardiographic evaluation of systolic heart failure.

Echocardiography is the most commonly used modality for evaluating left ventricular size and function in the context of systolic heart failure. Traditional techniques, though extensively used, have their limitations and more recently several newer technologies have emerged that are more reproducible, provide prognostic information, guide therapies and have an important role in monitoring progress. This review will evaluate the traditional and more novel techniques used and briefly provide an overview of the role of echocardiography in guiding and monitoring therapies in patients with systolic heart failure.

Empirical tests of the functional significance of amygdala-based modulation of hippocampal representations: evidence for multiple memory consolidation pathways.

This series of experiments evaluated the effects of amygdala damage on the acquisition and long-term retention of variants of the water task, and tested the hypothesis that the amygdala is an essential neural system for consolidation of hippocampal memories. In Experiment 1, rats with large, neurotoxic lesions of the amygdala (AMYG) showed normal acquisition on the standard spatial version of the water task, as well as normal retention and decay rate profiles on the 24-h and 30-day retention probes. In Experiment 2, AMYG rats showed normal one-trial place learning abilities and could retain this one-trial information over a 24 h delay. Experiment 3 showed that the amygdala lesions used in this study were functionally significant because AMYG rats, from Experiment 2, showed impairments in a discriminative fear conditioning to context paradigm. Experiment 4 was a critical test of the idea that the amygdala is a decisive locus for consolidation of hippocampal memories. AMYG rats were trained to sub-asymptotic levels of performance on the standard version of the water task. Following each training session, the subjects were given a post-training peripheral injection of D-amphetamine. A probe test revealed that normal subjects and AMYG rats showed similar post-training memory improvement effects. Taken together, the results show that hippocampal memory consolidation processes do not require amygdala modulation. Arguments for an alternative view are presented suggesting that there are multiple memory consolidation pathways, one of which may depend on amygdala neural circuitry.