Rodel Leano

Alterations of Left Ventricular Myocardial Characteristics Associated With Obesity

Background—Obesity is associated with heart failure, but an effect of weight, independent of comorbidities, on cardiac structure and function is not well established. We sought whether body mass index (BMI) and insulin levels were associated with subclinical myocardial disturbances. Methods and Results—Transthoracic echocardiography, myocardial Doppler-derived systolic (sm) and early diastolic velocity (em), strain and strain rate imaging and tissue characterization with cyclic variation (CVIB), and calibrated integrated backscatter (cIB) were obtained in 109 overweight or obese subjects and 33 referents (BMI <25 kg/m2). BMI correlated with left ventricular (LV) mass and wall thickness (P<0.001). Severely obese subjects (BMI >35) had reduced LV systolic and diastolic function and increased myocardial reflectivity compared with referents, evidenced by lower average long-axis strain, sm, cIB, lower CVIB, and reduced em, whereas LV ejection fraction remained normal. Differences in regional or global strain, sm, and em were identified between the severely obese (BMI >35) and the referent patients (P<0.001). Similar but lesser degrees of reduced function by sm, em, and basal septal strain and increased reflectivity by cIB were present in overweight (BMI, 25 to 29.9) and mildly obese (BMI, 30 to 35) groups (P<0.05). Although tissue Doppler measures were not associated with duration of obesity, they did correlate with fasting insulin levels and reduced exercise capacity. BMI was independently related to average LV strain (&bgr;=0.40, P=0.02), sm (&bgr;=−0.36, P=0.002), and em (&bgr;=−0.41, P<0.001). Conclusions—Overweight subjects without overt heart disease have subclinical changes of LV structure and function even after adjustment for mean arterial pressure, age, gender, and LV mass.

Prediction of all-cause mortality from global longitudinal speckle strain: comparison with ejection fraction and wall motion scoring.

Background—Although global left ventricular systolic function is an important determinant of mortality, standard measures such as ejection fraction (EF) and wall motion score index (WMSI) have important technical limitations. The aim of this study was to compare global longitudinal speckle strain (GLS), an automated technique for measurement of long-axis function, with EF and WMSI for the prediction of mortality. Methods and Results—Of 546 consecutive individuals undergoing echocardiography for assessment of resting left ventricular function, 91 died over a period of 5.2±1.5 years. In addition to Simpson biplane EF, WMSI was determined by 2 experienced readers and GLS was calculated from 3 standard apical views using 2D speckle tracking. The incremental value of EF, WMSI, and GLS to significant clinical variables was assessed in nested Cox models. Clinical factors associated with outcome (model &khgr;2=20.2) were age (hazard ratio [HR], 1.46; P<0.01), diabetes (HR, 1.88; P=0.01), and hypertension (HR, 1.59; P<0.05). Although addition of EF (HR, 1.23; P=0.03) or WMSI (HR, 1.28; P<0.01) added to the predictive power of clinical variables, the addition of GLS (HR, 1.45; P<0.001) caused the greatest increment in model power (&khgr;2=34.9, P<0.001). GLS also provided incremental value in subgroups with EF >35% and those with and without wall motion abnormalities. A GLS ≥−12% was found to be equivalent to an EF ≤35% for the prediction of prognosis. Intraobserver and interobserver variations for EF and GLS were similar. Conclusions—GLS is a superior predictor of outcome to either EF or WMSI and may become the optimal method for assessment of global left ventricular systolic function.Background— Although global left ventricular systolic function is an important determinant of mortality, standard measures such as ejection fraction (EF) and wall motion score index (WMSI) have important technical limitations. The aim of this study was to compare global longitudinal speckle strain (GLS), an automated technique for measurement of long-axis function, with EF and WMSI for the prediction of mortality. Methods and Results— Of 546 consecutive individuals undergoing echocardiography for assessment of resting left ventricular function, 91 died over a period of 5.2±1.5 years. In addition to Simpson biplane EF, WMSI was determined by 2 experienced readers and GLS was calculated from 3 standard apical views using 2D speckle tracking. The incremental value of EF, WMSI, and GLS to significant clinical variables was assessed in nested Cox models. Clinical factors associated with outcome (model χ2=20.2) were age (hazard ratio [HR], 1.46; P 35% and those with and without wall motion abnormalities. A GLS ≥−12% was found to be equivalent to an EF ≤35% for the prediction of prognosis. Intraobserver and interobserver variations for EF and GLS were similar. Conclusions— GLS is a superior predictor of outcome to either EF or WMSI and may become the optimal method for assessment of global left ventricular systolic function. Received March 9, 2009; accepted July 17, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Myocardial Strain Measurement With 2-Dimensional Speckle-Tracking Echocardiography: Definition of Normal Range

The interpretation of wall motion is an important component of echocardiography but remains a source of variation between observers. It has been believed that automated quantification of left ventricular (LV) systolic function by measurement of LV systolic strain from speckle-tracking echocardiography might be helpful. This multicenter study of nearly 250 volunteers without evidence of cardiovascular disease showed an average LV peak systolic strain of -18.6 +/- 0.1%. Although strain was influenced by weight, blood pressure, and heart rate, these features accounted for only 16% of variance. However, there was significant segmental variation of regional strain to necessitate the use of site-specific normal ranges.

Effect of Aldosterone Antagonism on Myocardial Dysfunction in Hypertensive Patients With Diastolic Heart Failure

Background—Specific treatments targeting the pathophysiology of hypertensive heart disease are lacking. As aldosterone has been implicated in the genesis of myocardial fibrosis, hypertrophy, and dysfunction, we sought to determine the effects of aldosterone antagonism on myocardial function in hypertensive patients with suspected diastolic heart failure by using sensitive quantitative echocardiographic techniques in a randomized, double-blinded, placebo-controlled study. Methods and Results—Thirty medically treated ambulatory hypertensive patients (19 women, age 62±6 years) with exertional dyspnea, ejection fraction >50%, and diastolic dysfunction (E/A <1, E deceleration time >250m/sec) and without ischemia were randomized to spironolactone 25 mg/d or placebo for 6 months. Patients were overweight (31±5 kg/m2) with reduced treadmill exercise capacity (6.7±2.1 METS). Long-axis strain rate (SR), peak systolic strain, and cyclic variation of integrated backscatter (CVIB) were averaged from 6 walls in 3 standard apical views. Mean 24-hour ambulatory blood pressure at baseline (133±17/80±7mm Hg) did not change in either group. Values for SR, peak systolic strain, and CVIB were similar between groups at baseline and remained unchanged with placebo. Spironolactone therapy was associated with increases in SR (baseline: −1.57±0.46 s−1 versus 6-months: −1.91±0.36 s−1, P<0.01), peak systolic strain (−20.3±5.0% versus −26.9±4.3%, P<0.001), and CVIB (7.4±1.7dB versus 8.6±1.7 dB, P=0.08). Each parameter was significantly greater in the spironolactone group compared with placebo at 6 months (P=0.05, P=0.02, and P=0.02, respectively), and the increases remained significant after adjusting for baseline differences. The increase in strain was independent of changes in blood pressure with intervention. The spironolactone group also exhibited reduction in posterior wall thickness (P=0.04) and a trend to reduced left atrial area (P=0.09). Conclusions—Aldosterone antagonism improves myocardial function in hypertensive heart disease.

Relationship between longitudinal and radial contractility in subclinical diabetic heart disease

Subclinical left ventricular (LV) dysfunction may be identified by reduced longitudinal contraction. We sought to define the effects of subclinical LV dysfunction on radial contractility in 53 patients with diabetes mellitus with no LV hypertrophy, normal ejection fraction and no ischaemia as assessed by dobutamine echocardiography, in comparison with age-matched controls. Radial peak myocardial systolic velocity (Sm) and early diastolic velocity (Em), strain and strain rate were measured in the mid-posterior and mid-anteroseptal walls in parasternal views and each variable was averaged for individual patients (radial contractility). These variables were also measured in the mid-posterior and mid-anteroseptal walls in the apical long-axis view and each variable was averaged for individual patients (longitudinal contractility). Mean radial Sm, strain and strain rate were significantly increased in diabetic patients (2.9 +/- 0.6 cm/s, 28 +/- 5% and 1.8 +/- 0.4 s(-1) respectively) compared with controls (2.4 +/- 0.7 cm/s, 23 +/- 4% and 1.6 +/- 0.3 s(-1) respectively; all P<0.001), but there was no difference in Em (3.3 +/- 1.2 compared with 3.1 +/- 1.1 cm/s, P=not significant). In contrast, longitudinal Sm, Em, strain and strain rate were significantly lower in diabetic patients (3.6 +/- 1.1 cm/s, 4.3 +/- 1.6 cm/s, 21 +/- 4% and 1.6 +/- 0.3 s(-1) respectively) than in controls (4.3 +/- 1.0 cm/s, 5.7 +/- 2.3 cm/s, 26 +/- 4% and 1.9 +/- 0.3 s(-1) respectively; all P< or =0.001). Thus radial contractility appears to compensate for reduced longitudinal contractility in subclinical LV dysfunction occurring in the absence of ischaemia or LV hypertrophy.

Use of myocardial deformation imaging to detect preclinical myocardial dysfunction before conventional measures in patients undergoing breast cancer treatment with trastuzumab

BACKGROUND Trastuzumab prolongs survival in patients with human epidermal growth factor receptor type 2-positive breast cancer. Sequential left ventricular (LV) ejection fraction (EF) assessment has been mandated to detect myocardial dysfunction because of the risk of heart failure with this treatment. Myocardial deformation imaging is a sensitive means of detecting LV dysfunction, but this technique has not been evaluated in patients treated with trastuzumab. The aim of this study was to investigate whether changes in tissue deformation, assessed by myocardial strain and strain rate (SR), are able to identify LV dysfunction earlier than conventional echocardiographic measures in patients treated with trastuzumab. METHODS Sequential echocardiograms (n = 152) were performed in 35 female patients (51 +/- 8 years) undergoing trastuzumab therapy for human epidermal growth factor receptor type 2-positive breast cancer. Left ventricular EF was measured by 2- and 3-dimensional (2D and 3D) echocardiography, and myocardial deformation was assessed using tissue Doppler imaging and 2D-based (speckle-tracking) strain and SR. Change over time was compared every 3 months between baseline and 12 months. RESULTS There was no overall change in 3D-EF, 2D-EF, myocardial E-velocity, or strain. However, there were significant reductions seen in tissue Doppler imaging SR (P < .05), 2D-SR (P < .001), and 2D radial SR (P < .001). A drop > or =1 SD in 2D longitudinal SR was seen in 18 (51%) patients; 13 (37%) had a similar drop in radial SR. Of the 18 patients with reduced longitudinal SR, 3 had a concurrent reduction in EF > or =10%, and another 2 showed a reduction over 20 months follow-up. CONCLUSIONS Myocardial deformation identifies preclinical myocardial dysfunction earlier than conventional measures in women undergoing treatment with trastuzumab for breast cancer.

Relation of arterial stiffness to diastolic dysfunction in hypertensive heart disease

Objectives: To examine the relation of arterial compliance to diastolic dysfunction in hypertensive patients with suspected diastolic heart failure (HF). Patients: 70 medically treated hypertensive patients with exertional dyspnoea (40 women, mean (SD) age 58 (8) years) and 15 normotensive controls. Main outcome measures: Mitral annular early diastolic velocity with tissue Doppler imaging and flow propagation velocity were used as linear measures of diastolic function. Arterial compliance was determined by the pulse pressure method. Results: According to conventional Doppler echocardiography of transmitral and pulmonary venous flow, diastolic function was classified as normal in 33 patients and abnormal in 37 patients. Of those with diastolic dysfunction, 28 had mild (impaired relaxation) and nine had advanced (pseudonormal filling) dysfunction. Arterial compliance was highest in controls (mean (SD) 1.32 (0.58) ml/mm Hg) and became progressively lower in patients with hypertension and normal function (1.04 (0.37) ml/mm Hg), impaired relaxation (0.89 (0.42) ml/mm Hg), and pseudonormal filling (0.80 (0.45) ml/mm Hg, p  =  0.011). In patients with diastolic dysfunction, arterial compliance was inversely related to age (p  =  0.02), blood pressure (p < 0.001), and estimated filling pressures (p < 0.01) and directly related to diastolic function (p < 0.01). After adjustment for age, sex, body size, blood pressure, and ventricular hypertrophy, arterial compliance was independently predictive of diastolic dysfunction. Conclusions: In hypertensive patients with exertional dyspnoea, progressively abnormal diastolic function is associated with reduced arterial compliance. Arterial compliance is an independent predictor of diastolic dysfunction in patients with hypertensive heart disease and should be considered a potential target for intervention in diastolic HF.

Feasibility and Accuracy of Different Techniques of Two-Dimensional Speckle Based Strain and Validation With Harmonic Phase Magnetic Resonance Imaging

BACKGROUND Different 2-dimensional speckle-based strain techniques have been developed to overcome the problem of angle dependency with Doppler-based strain. However, their relative accuracy has not been assessed. The aim of this study was to determine the feasibility and accuracy of 2 such techniques (velocity vector imaging [VVI] and automated function imaging [AFI]), using tagged harmonic phase (HARP) magnetic resonance imaging (MRI) as a reference standard. METHODS Thirty patients with known or suspected ischemic heart disease underwent measurement of peak systolic longitudinal, radial, and circumferential Lagrangian strain with all 3 techniques using a 16-segment model. The extent of scar tissue in each segment was determined using contrast-enhanced MRI. RESULTS The measurement of myocardial strain in all 3 directions was highly feasible with both VVI and AFI. Longitudinal strain was underestimated by both VVI (-11 +/- 8%; P < .01) and AFI (-12 +/- 6%; P < .01) in comparison with HARP MRI (-14 +/- 5%), and radial strain was underestimated by VVI (14 +/- 18% vs 23 +/- 7%; P < .01). All strain measurements with AFI showed better correlation and agreement with HARP MRI compared with VVI. Circumferential strain with AFI had the greatest accuracy (area under the receiver operating characteristic curve = 0.74, P < .001) for the prediction of scar tissue on MRI. CONCLUSIONS Two-dimensional strain measured with AFI has significantly better accuracy than VVI. Circumferential strain with AFI has the best discriminative ability for the detection of regional myocardial dysfunction.

Clinical Assessment of Left Ventricular Systolic Torsion: Effects of Myocardial Infarction and Ischemia

BACKGROUND The helical arrangement of myocardial fibers leads to left ventricular (LV) torsion, a vital contributor to systolic and diastolic function. Rotation and torsion can now be measured; we sought to determine the utility of torsion as a marker of LV function at rest and after stress in patients with myocardial infarctions (MIs) and ischemia. METHODS Dobutamine echocardiography was performed in 125 patients. After the exclusion of 40 patients with suboptimal images, LV systolic rotation and torsion were measured offline using speckle-tracking echocardiography in 44 patients with and 41 without prior MIs. Hemodynamic findings and the extent of infarction and ischemia were correlated with length-corrected torsion measurements at baseline and at peak-dose dobutamine. RESULTS Resting global and regional LV systolic torsion were significantly reduced in patients with compared with those without previous MIs (1.16 +/- 1.15 degrees /cm vs 3.16 +/- 1.3 degrees /cm, P < .001), and global systolic torsion was an independent correlate of LV ejection fraction (LVEF) (P = .04). There was no difference in global LV systolic torsion in patients with anteroapical or inferoposterior infarcts (1.81 +/- 1.13 degrees /cm vs 2.27 +/- 1.18 degrees /cm, P = NS) and no differences in regional torsion. Torsion was most impaired in patients with multiple areas of infarction (1.03 +/- 0.89 degrees /cm, P < .001). However, dobutamine-induced ischemia (2.59 +/- 1.14 ischemic segments) had no effect on global and regional systolic torsion at peak dose or change in torsion from rest to peak dose. CONCLUSIONS The influence of MI on LV systolic torsion appears to be related to infarct size rather than site, and torsion was an independent determinant of resting function. LV torsion was not significantly influenced by stress-induced myocardial ischemia.

Assessment of Myocardial Viability at Dobutamine Echocardiography by Deformation Analysis Using Tissue Velocity and Speckle-Tracking

OBJECTIVES Comparison of myocardial tissue-velocity imaging (TVI) and speckle-tracking echocardiography (STE) for prediction of viability at dobutamine echocardiography (DbE). BACKGROUND Use of TVI-based strain imaging during DbE may facilitate the prediction of myocardial viability but has technical limitations. STE overcomes these but requires evaluation for prediction of viability. METHODS We studied 55 patients with ischemic heart disease and left ventricular systolic dysfunction (left ventricular ejection fraction <0.45) who were undergoing DbE for assessment of myocardial viability and who subsequently underwent myocardial revascularization. TVI was used to measure longitudinal end-systolic strain (longS) and peak systolic strain rate (SR) at rest and at low-dose dobutamine (LDD). Longitudinal, radial, and circumferential strain and strain rate were measured with STE. Segmental functional recovery was defined by improved wall-motion score on side-by-side comparison of echocardiographic images before and 9 months after revascularization and areas under the receiver operator characteristic curves were used to compare methods. RESULTS Of the 375 segments with abnormal resting function, 154 (41%) showed functional recovery. Only circumferential resting and low-dose STE strain and low-dose longitudinal strain and SR predicted functional recovery independent of wall-motion analysis. Among different strain parameters, only TVI-based longitudinal end-systolic strain and peak systolic SR at LDD had incremental value over wall-motion analysis (areas under the receiver operator characteristic curves of 0.79, 0.79, and 0.74, respectively). STE measurements of strain and SR identified viability only in the anterior circulation, whereas TVI strain and SR accurately identified viability in both anterior and posterior circulations. CONCLUSIONS Combination of TVI or STE methods with DbE can predict viability, with TVI strain and SR at LDD being the most accurate. TVI measures can predict viability in both anterior and posterior circulations, but STE measurements predict viability only in the anterior circulation.