Gerard King

Subclinical anthracycline- and trastuzumab-induced cardiotoxicity in the long-term follow-up of asymptomatic breast cancer survivors: a speckle tracking echocardiographic study

Objective To examine the long-term effects of standard chemotherapy on myocardial function in asymptomatic breast cancer survivors using two-dimensional speckle tracking echocardiography. Methods Seventy women (chemotherapy group) aged 54±8 years who had received anthracycline treatment with (n=19) or without (n=51) adjuvant trastuzumab up to 6 years previously, and 50 female controls were studied. Left ventricular systolic (ejection fraction (EF%), peak systolic myocardial excursion, (Sm)) and diastolic (peak mitral E and A velocities, six-point average of mitral annular E′ velocities) function, 2D global and regional longitudinal and radial strain were determined using standard 2D Doppler and tissue Doppler echocardiographic methods and speckle tracking software. Results Despite normal EF% (62±4% vs 60±3%, p=0.051) the chemotherapy group had reduced E/A ratios (0.9±0.3 vs 1.1±0.3, p=0.003), global E′ (10.2±2 vs 11.2±2.3, p=0.036), global Sm (9.0±1.3 vs 9.6±1.3, p=0.029) and global longitudinal 2D strain (−18.1±2.2 vs −19.6±1.8, p=0.0001) in comparison with controls. In 18 (26%) of the chemotherapy group, global longitudinal strain was below the lower limit of the control group. Cigarette smoking was a negative predictor of longitudinal strain, but only in the chemotherapy group. Radial strain did not differ significantly between the two groups. There were no significant differences in EF%, global Sm and longitudinal strain between trastuzumab-treated individuals and controls. Conclusions Subclinical systolic and diastolic myocardial abnormalities were present in asymptomatic breast cancer survivors up to 6 years after standard chemotherapy. Cigarette smoking had a negative effect on longitudinal strain in these individuals. Adjuvant trastuzumab treatment did not appear to have an additive adverse impact on myocardial function in the medium–long term.

Alterations in Myocardial Stiffness in Elite Athletes assessed by a new Doppler Index

Background: In elite athletes left ventricular (LV) morphological changes are predicted to alter passive pressure/volume characteristics by reducing myocardial stiffness and increasing compliance. Objective: To investigate the utility of a new Doppler tissue index based on the pressure volume relation ((E/Ea)/LVEDD), which provides a measure of myocardial stiffness, and to assess its usefulness in detecting cardiac adaptation in elite rowers. Methods: Thirty-six international rowers who had trained intensively and a control group of 30 sedentary subjects, matched for age and sex, were enrolled in the study. LV septal and posterior wall thickness, mass, chamber size, transmitral Doppler peak early (E) and late (A) diastolic filling velocities and isovolumic relaxation times were measured. Early diastolic myocardial velocities (Ea) were averaged from four sites at the mitral annulus; diastolic stiffness was assessed with the use of three indices E, Ea and the LV end-diastolic diameter in diastole (LVEDD). The ratio, (E/Ea)/LVEDD, provides a new index of diastolic stiffness. Rowers were further divided into two groups based on the presence or absence of left ventricular hypertrophy (LVH) ⩽12 mm and >12 mm. Results: No significant difference in Ea was found between the two groups, but there was a difference in the stiffness index, which remained after adjustment for body surface area and heart rate (controls 1.48 (0.3) vs athletes 1.17 (0.34), p = 0.016). No difference in stiffness index was found between the groups with LVH ⩽12 mm and >12 mm (1.11 (0.32) vs 1.17 (0.34), respectively, p = 0.68) Conclusions: Intense training reduces myocardial stiffness despite the development of LVH.

Left ventricular structural and functional changes in the metabolic syndrome.

To test the hypothesis that the cardiac structural and functional abnormalities of the metabolic syndrome (MS) are independent of body mass index (BMI), 160 untreated patients (aged 47+/-1 years [mean +/- SEM], 53% male) underwent 2-dimensional echocardiography and tissue Doppler imaging and evaluation for MS. Participants with MS and controls were similar in age, BMI, and ejection fraction, but those with MS had greater left ventricular relative wall thickness (RWT) (0.43+/-0.008 vs 0.39+/-0.005, P<.001), reduced midwall fractional shortening (MFS) (13%+/-0.3% vs 14.2%+/-0.3%, P<.05), and reduced peak mitral annular velocity (Em) (9.9+/-0.5 vs 12.3+/-0.5 cm/sec, P<.01) than controls. There was a linear relationship between the number of features of MS and Em velocity (P<.001), RWT (P<.001), and MFS (P<.05). In a stepwise multiple regression analysis adjusting for likely determinants, MS was an independent predictor of Em in addition to age and nonindexed left ventricular mass. MS is associated with left ventricular concentric remodeling and reduced systolic and diastolic function independent of BMI.

Reduced right ventricular myocardial strain in the elite athlete may not be a consequence of myocardial damage. "Cream masquerades as skimmed milk".

Latest research shows that the lower resting values of right ventricular (RV) myocardial % strain may represent a physiologic change rather than subclinical myocardial damage. Therefore, we assessed load‐independent changes to the RV as a consequence of high intensity training by measuring the Isovolumic acceleration (IVA) of the free wall of the RV in conjunction with NT pro‐BNP measured by an electrochemiluminescence assay.

Early diastolic filling dynamics in diastolic dysfunction.

BackgroundThe aim of the study was to determine the relationship between the rate of peak early mitral inflow velocity and the peak early diastolic mitral annular tissue velocities in normal controls and to compare them with subjects with diastolic dysfunction.MethodsThe relationship between early passive diastolic transmitral flow and peak early mitral annular velocity in the normal and in diastolic dysfunction was studied. Two groups comprising 22 normal controls and 25 patients with diastolic dysfunction were studied.ResultsCompared with the normal group, those with diastolic dysfunction had a lower E/A ratio (0.7 ± 0.2 vs. 1.9 ± 0.5, p < 0.001), a higher time-velocity integral of the atrial component (11.7 ± 3.2 cm vs. 5.5 ± 2.1 cm, p < 0.0001), a longer isovolumic relaxation time 73 ± 12 ms vs. 94 ± 6 ms, p < 0.01 and a lower rate of acceleration of blood across the mitral valve (549.2 ± 151.9 cm/sec2 vs. 871 ± 128.1 cm/sec2, p < 0.001). They also had a lower mitral annular relaxation velocity (Ea) (6.08 ± 1.6 cm/sec vs 12.8 ± 0.67 cm/sec, p < 0.001), which was positively correlated to the acceleration of early diastolic filling (R = 0.66), p < 0.05.ConclusionsThis investigation provides information on the acceleration of early diastolic filling and its relationship to mitral annular peak tissue velocity (Ea) recorded by Doppler tissue imaging. It supports not only the premise that recoil is an important mechanism for rapid early diastolic filling but also the existence of an early diastolic mechanism in normal.

664 Early diastolic filling dynamics in patients with diastolic dysfunction.

0.66, p< 0.05). The normal group did not show a correlation between the acceleration of transmitral flow and mitral annular relaxation velocity (r=0.18, p < 0.22). Those with diastolic dysfunction also had a lower E/A ratio than the normal group (0.7 ± 0.2 vs. 1.9 ± 0.5, p < 0.001), a higher time-velocity integral of the atrial component (11.7 ± 3.2 cm vs. 5.5 ± 2.1 cm, p < 0.0001) and a lower rate of acceleration of blood across the mitral valve (549.2 ± 151.9 cm/sec2 vs. 871 ± 128.1cm/sec2 ,p <.001). Conclusions In diastolic dysfunction where the influence of preload is minimal, recoil and the acceleration of early diastolic blood flow are reduced compared to normals. Also the rate of flow across the mitral valve was found to be strongly related to mitral annular tissue velocity. This relationship reveals the influence of recoil on flow in diastolic dysfunction. However in normal subjects the acceleration of early diastolic blood flow and recoil are not correlated. Recoil in normal provides the potential energy for rapid early diastolic filling and occurs during isovolumic relaxation before filling. Therefore rapid early diastolic filling under the influence of preload occurs after isovolumic relaxation and no relationship exists. This supports the existence of an early diastolic mechanism in normal.