Speckle-Tracking Echocardiography for Monitoring Acute Rejection in Transplanted Heart.

BACKGROUND: The diagnosis of acute cellular rejection (ACR) is a major objective in the management of heart transplant recipients. The aim of this study was to assess the utility of speckle-tracking derived parameters in identifying patients at risk of graft rejection. METHODS: A prospective, single-center study was carried out involving 45 consecutive heart transplant patients who underwent a total of 220 routine endomyocardial biopsies (EMBs) with correlative echocardiographic examination. RESULTS: No significant ACR (grade 0-1R) was seen in 190 biopsies (81.2% of the ACR-free group), and moderate ACR requiring specific treatment (grade 2R) was detected in 30 biopsies (13.6% of the ACR group). Grade 3R was not observed. All longitudinal left ventricular (LV) and right ventricular (RV) strain parameters were greater in the ACR-free group than in patients with ACR, while no differences were observed between radial and circumferential strain parameters. In our analysis, we selected RV free wall longitudinal strain (RV FW) ≤ 16.8% and 4-chamber longitudinal strain (4CH LS) ≤ 13.8%, which related to the presence of ACR requiring treatment. We assigned 1 point for each parameter (minimum 0, maximum 2 points) and derived a new echocardiographic index, the Strain Rejection Score (SRS). Our proposed approach-a combination of the 2 abovementioned indices-for screening patients at risk of ACR ≥ 2R, when expressed by a score 2 points, showed good specificity, strong negative predictive value, and the highest area under the curve. CONCLUSIONS: Our study demonstrated that combination of 4CH LS and RV FW as a new echocardiographic index, the Strain Rejection Score, can be useful as a noninvasive assessment of ACR during the first year of follow-up after heart transplant.

LV mechanical dispersion as a predictor of ventricular arrhythmia in patients with advanced systolic heart failure : A pilot study.

BACKGROUND: Myocardial mechanical dyssynchrony induced by the presence of postinfarction scar and/or conduction abnormalities in patients with a left ventricular ejection fraction (LVEF) of < 35 % may be associated with a greater propensity toward inducing serious ventricular arrhythmia [(ventricular tachycardia (VT), ventricular fibrillation (VF)] and sudden cardiac death. The assessment of regional myocardial function using tissue Doppler echocardiography (TDE) allows for noninvasive analysis of regional mechanical dysfunction (LV mechanical dispersion). AIM: The aim of this study was to evaluate the TDE-based mechanical dispersion as a potential echocardiographic predictor of VT/VF. METHODS: The study group consisted of 47 consecutive ambulatory patients with implanted cardiac resynchronization therapy-defibrillator (CRT-D) devices who were divided into two groups: Group 1 (n = 29) comprised patients with recorded episodes of VT/VF, in whom baseline TDE data were available, and group 2 (n = 18) comprised patients without registered VT/VF in the device memory within 4 years after implantation. LV mechanical dispersion was defined as the standard deviation of the time measured from the beginning of the QRS complex to the peak longitudinal strain in apical four-chamber and two-chamber views. A retrospective quantitative assessment of LV regional deformation was based on the color tissue velocity recordings. RESULTS: The average time to event after implantation was 345 days. Patients with electrical events demonstrated greater mechanical dispersion: 99.14 ± 33.60 vs. 72.98 ± 19.70, p=0.002. CONCLUSION: During the 4-year follow-up, patients with documented VT/VF were characterized by significantly higher LV mechanical dispersion as compared with patients without electrical events. Measurement of LV mechanical dispersion might be helpful in determining the risk of sudden cardiac death.

Right ventricular function in patients with severe interstitial lung disease: a Tissue Doppler imaging study.

Tissue Doppler imaging (TDI) can be useful in the evaluation of right ventricular (RV) regional dysfunction due to pulmonary diseases. The aim of the study was to assess RV dysfunction in patients with severe interstitial lung diseases (ILD), using both TDI and conventional transthoracic echocardiography (TTE). The study group consisted of 40 consecutive patients with end-stage ILD referred for lung transplantation (LT). Eighteen of them, mean age 47 +/-12 yr, who fulfilled the ATS/ERS criteria for LT (mean forced vital capacity (FVC) 1.4 +/-0.8 l, mean diffusing capacity for carbon dioxide (DLCO) <50% of predicted) constituted the active group, and 22 age-matched patients (mean age 49 +/-12 yr), who did not fulfill these criteria, were placed in the waiting group for LT. We found that among the TDI parameters, the longitudinal peak systolic strain rate (SR) measured at the RV outflow tract, was significantly more negative (-1.1 +/-0.3 vs. -3.2 +/-1.2 s(-1), P=0.03) and the time to peak velocity (TpVEL) in the medial and apical septal segments were shorter (129.9 +/-47.9 vs. 159.2 +/-38.1 ms, P=0.018 and 126.8 +/-44.3 vs. 154.6 +/-40.9 ms, P=0.019) in the patients from the active than those from the waiting group. TTE showed that patients from the active group had significantly lower values of tricuspid annulus plane systolic excursion (TAPSE) (14.3 +/-3.3 vs. 20.6 +/-6.2 mm, P=0.0003) and pulmonary artery acceleration time (PVAT) (70.3 +/-23.3 vs. 96.9 +/-12.4 ms, P=0.0001)compared with those from the waiting group. No other differences were found for other parameters of RV function between the examined groups. In conclusion, severity of lung disease in patients with ILD influences RV systolic dysfunction, which is reflected in both TDI and conventional echocardiographic parameters.

Polymorphisms in adenosine receptor genes are associated with infarct size in patients with ischemic cardiomyopathy.

The goal of this experiment was to identify the presence of genetic variants in the adenosine receptor genes and assess their relationship to infarct size in a population of patients with ischemic cardiomyopathy. Adenosine receptors play an important role in protecting the heart during ischemia and in mediating the effects of ischemic preconditioning. We sequenced DNA samples from 273 individuals with ischemic cardiomyopathy and from 203 normal controls to identify the presence of genetic variants in the adenosine receptor genes. Subsequently, we analyzed the relationship between the identified genetic variants and infarct size, left ventricular size, and left ventricular function. Three variants in the 3'-untranslated region of the A(1)-adenosine gene (nt 1689 C/A, nt 2206 Tdel, nt 2683del36) and an informative polymorphism in the coding region of the A3-adenosine gene (nt 1509 A/C I248L) were associated with changes in infarct size. These results suggest that genetic variants in the adenosine receptor genes may predict the heart's response to ischemia or injury and might also influence an individual's response to adenosine therapy.

Quantification of the spectrum of changes in regional myocardial function during acute ischemia in closed chest pigs: an ultrasonic strain rate and strain study.

The objectives of this study were to define the spectrum of regional myocardial function changes during acute ischemia in closed chest animals by using newly developed ultrasonic strain rate and strain indexes derived from regional color Doppler myocardial imaging (CDMI) velocity data. Myocardial ischemia was induced in 18 pigs either with acute total 20-second occlusions (group 1, n = 12) or graded hypoperfusion (40 to 0 mL/min, group 2, n = 6) of the circumflex coronary artery. In addition, a dobutamine challenge (5 to 10 microg/kg per minute) was performed during sustained subtotal ischemia (10 mL/min) in group 2. CDMI acquisitions with parasternal views monitored the myocardial posterior wall function. Regional radial strain rate and strain (epsilon(r)) were measured for systole, isovolumic relaxation, early diastole, and atrial filling, respectively. During total and graded ischemia, epsilon(r) profiles were consistently modified, showing a delayed onset and a decrease in regional systolic thickening as well as increased postsystolic thickening. Radial strain rate and epsilon(r) indexes decreased consistently during systole and early diastole and increased during isovolumic relaxation. End-systolic epsilon(r) could differentiate total ischemia from severe hypoperfusion (10 mL/min), decreasing from 32% +/- 8% to 16% +/- 5% (versus 60% +/- 10% at baseline). During dobutamine infusion (10 microg/kg per minute), end-systolic epsilon(r) tended to decrease from 27% +/- 5% to 18% +/- 11%, whereas postsystolic thickening increased by 2-fold (P <.05). The combined analysis of regional deformation characteristics and global cardiac event timing derived from CDMI data can identify and quantify regional function changes induced by experimental acute ischemia in closed chest pigs. This would appear to be a potentially promising new noninvasive approach to the clinical evaluation of ischemia-induced changes in segmental myocardial function.

Can natural strain and strain rate quantify regional myocardial deformation? A study in healthy subjects.

Strain rate (SR) and strain (epsilon) have been proposed as new ultrasound (US) indices for quantifying regional wall deformation, and can be measured from color Doppler myocardial data by determining the local spatial velocity gradient. The aim of this study was to define normal regional SR/epsilon values for both radial and longitudinal myocardial deformation. SR/epsilon profiles were obtained from 40 healthy volunteers. For radial deformation, posterior left ventricular (LV) wall SR/epsilon were calculated. For longitudinal, they were determined for basal, mid- and apical segments of the 1. septum; 2. lateral, 3. posterior and 4. anterior LV walls and for the 5. right ventricular (RV) lateral wall. SR/epsilon values describing radial deformation were higher than the corresponding SR/epsilon values obtained for longitudinal deformation. Longitudinal SR/epsilon were homogeneous throughout the septum and all LV walls. This was in contrast to the normal base-apex velocity gradient. The RV segmental SR/epsilon values were higher than those obtained from the corresponding LV wall and inhomogeneous (higher in the apical segments). SR/epsilon imaging appears to be a robust technique for quantifying regional myocardial deformation.

Noninvasive quantification of the contractile reserve of stunned myocardium by ultrasonic strain rate and strain.

BACKGROUND: We sought to investigate ultrasonic strain rate and strain as new indices to quantify the contractile reserve of stunned myocardium during dobutamine infusion. METHODS AND RESULTS: Stunning of the left ventricular posterior wall was induced in 9 closed-chest pigs after 30 minutes of severe hypoperfusion followed by 60 minutes of reperfusion of the left circumflex coronary artery territory. A second group of 7 animals had no coronary occlusion and served as normal controls. An incremental dobutamine infusion protocol was used in both groups. Changes in regional radial function were monitored by use of ultrasound-derived maximal systolic radial strain rate (SR) and systolic strain (epsilon). In the control group, dobutamine induced an increase in both SR and maximal dP/dt, which correlated linearly (r=0.85). Conversely, epsilon values increased at low doses of dobutamine (2.5 to 5 microg. kg(-1). min(-1)) but decreased during higher infusion rates (10 to 20 microg. kg(-1). min(-1)). During circumflex hypoperfusion, SR and epsilon of the posterior wall decreased from 5.0+/-0.3 s(-1) and 63+/-6% to 2.9+/-0.3 s(-1) and 27+/-4%, respectively (P<0.01). After 60 minutes of reperfusion, SR and epsilon failed to fully resume because of stunning, averaging 3.6+/-0.2 s(-1) and 35+/-3%, respectively (P=0.12 versus ischemia, P<0.05 versus baseline). During dobutamine infusion, SR increased at 5 microg. kg(-1). min(-1) and exceeded baseline values at 20 microg. kg(-1). min(-1) (P<0.05), whereas epsilon increased only at high doses and remained below baseline levels (P<0.05). CONCLUSIONS: The changes in regional function of stunned myocardium during inotropic stimulation could be characterized by use of ultrasonic deformation parameters. During dobutamine infusion, strain-rate values quantified the contractile reserve better than strain values.

Changes in systolic and postsystolic wall thickening during acute coronary occlusion and reperfusion in closed-chest pigs: Implications for the assessment of regional myocardial function.

The aim of the study was to characterize the impact of short-lived total coronary occlusions in closed-chest pigs on radial wall thickening within the "at-risk" myocardial segment by using gray-scale M-mode echocardiography. Twelve pigs underwent a series of 20-second total circumflex coronary artery occlusions with an angioplasty balloon. Myocardial thickening/thinning indexes were continuously monitored before ischemia, during ischemia, and on reperfusion by high-resolution M-mode recordings of the posterior wall obtained from parasternal views. The timing of regional events was compared with global systolic time intervals derived from the color Doppler myocardial imaging velocity data. Each occlusion induced a rapid decrease in end-systolic thickening (epsilon(ES)), closely paralleled by an increase in postsystolic thickening in the ischemic segment. After 20 seconds of ischemia, epsilon(ES) decreased by -86% and postsystolic thickening increased by +100%, whereas maximal thickening decreased only by -34% in comparison with preocclusion values. All wall thickening parameters returned to baseline after 15 seconds of reperfusion. During acute total ischemia in a closed-chest animal model, the changes in regional myocardial function were best characterized by the combined analysis of systolic and postsystolic thickening abnormalities and by their respective timings relative to global cardiac events markers.

Does atrioventricular ring motion always distinguish constriction from restriction? A Doppler myocardial imaging study.

Constrictive pericarditis and restrictive cardiomyopathy can be difficult to differentiate on clinical examination. Cardiac ultrasonography is increasingly being used as the noninvasive method of choice for confirming the specific morphologic and hemodynamic abnormalities associated with either condition. Interrogation of atrioventricular valve plane motion by Doppler myocardial imaging (DMI) has been suggested as a valuable new approach that can help differentiate one from the other. We report the color DMI, pulsed DMI, and strain rate findings in 2 cases of constrictive pericarditis in which consideration of the annular motion pattern alone would not have allowed such differentiation.

Doppler myocardial imaging in the assessment of regional myocardial function in longitudinal direction pre- and post-PTCA.

AIMS: Doppler myocardial imaging is potentially a sensitive tool to assess regional myocardial velocities pre- and post-percutaneous transluminal coronary angioplasty (PTCA) as a marker of contractility to evaluate short- to medium-term information on functional myocardial recovery following the release of ischaemia. METHODS: Thirty patients with single vessel disease were studied to assess regional myocardial peak systolic velocity, systolic velocity time integral and mitral valve plane excursion in longitudinal direction one day pre-, one day post- and 3 months post-PTCA. The patients were assigned to group A with coronary stenoses >70% and group B with stenoses < 70%. RESULTS: In group A pre-PTCA the ischaemic segments showed a significantly lower peak systolic velocity and velocity time integral compared with the values one day after PTCA (5.8 +/- 1.4 vs 7.7 +/- 1.4cm.s(-1); 1.06 +/- 0.22 vs 1.23 +/-0.28cm;P< 0.03). In contrast, mitral valve plane excursion in this group remained unchanged after PTCA for both the ischaemic and non-ischaemic left ventricular wall. In group B no changes of these parameters and no differences in mitral valve plane excursion of the ischaemic and the non-ischaemic left ventricular wall could be seen. CONCLUSION: With Doppler myocardial imaging it was possible to quantify a number of indices which changed due to the successful release of ischaemia.

A comparison of regional myocardial velocity information derived by pulsed and color Doppler techniques: an in vitro and in vivo study.

The objective was to compare velocity information derived from either a tissue mimicking phantom or normal contracting myocardium by both pulsed wave and color Doppler myocardial imaging (PWDMI and CDMI). Both CDMI and PWDMI allow quantitative assessment of regional myocardial contraction and relaxation velocities, but their potential clinical applications have not yet been investigated. Moreover, no information is available as to whether they can be used interchangeably for regional velocity assessment. For the in vitro study, a rotating, circular-shaped, tissue-mimicking sponge driven by a motor at speeds of 15, 30, 60, 90 rpm was used to derive velocity data from the same eight points of interest by using PWDMI or CDMI techniques. For the in vivo study, 25 normal subjects were examined at rest using parasternal and apical approaches. Velocity profiles were derived from the same 26 areas of interest (18 left ventricular segments, 3 right ventricular segments, and 5 measurement points for the tricuspid and mitral annuli) for each technique. Peak maximal velocities were detected by PWDMI and peak mean velocities were measured using CDMI. The results of the in vitro study phantom showed excellent correlation (r = 0.99, P < 0. 001) and satisfactory agreement (0.04 cm/sec; 3.3 cm/sec) between both Doppler techniques. PWDMI velocities were higher than CDMI velocities by up to 20% and overestimated the real velocity value (0. 37 +/- 0.29 cm/sec) while CDMI underestimated predicted velocity by 1.35 +/- 0.36 cm/sec. Good correlation (r = 0.87, P < 0.001), but poor agreement (-2.1 cm/sec; 5.4 cm/sec) was shown in vivo for all segments with regard to peak systolic and diastolic velocities. Both Doppler techniques cannot be used interchangeably for comparing peak velocities in the clinical situation. However, with adequate temporal resolution, they can be used interchangeably for velocity profile recording and for timing of events.

Quantitation of left-ventricular asynergy by cardiac ultrasound.

The clinical evaluation of regional delays in myocardial motion (myocardial asynchrony) has proved problematic, yet it remains an important functional parameter to evaluate. Prior attempts to quantify regional asynergy have met with limited success, often thwarted by the low temporal resolution of imaging-system data acquisition. If a delay in onset of motion of 30-40 msec is clinically important to measure, then data acquisition at frame rates of 50-100 per second is required. This is out of the current temporal resolution of angiographic, nuclear, or magnetic resonance studies. Only cardiac ultrasound can currently achieve the necessary frame rates. Furthermore, quantitative studies into the accuracy with which a trained observer can identify computed regional myocardial asynchrony in a left-ventricular 2-dimensional (2-D) image have shown that regional delays of < 80 msec are not normally recognized in a moving image. This may be improved to 60 msec when either training is undertaken or comparative image review is used. However, this is still out of the temporal resolution required in clinical practice. Thus, visual interpretation of asynchrony is not sufficiently accurate. Two ultrasound data sets based on either integrated backscatter or Doppler myocardial imaging data may provide the solution. Doppler myocardial imaging is a new ultrasound technique which, in either its pulsed or color Doppler format, can achieve the required temporal resolution (with temporal resolutions of 8 msec and 16 msec, respectively). In contrast, color Doppler myocardial imaging, in its curved M-mode format, can display the timing of events during the cardiac cycle for all in-plane myocardial segments. This should allow the quantitation of regional delay for all systolic and diastolic events. Potentially, asynchrony due to regional ischemia, bundle branch block, ventricular premature beats, and ventricular preexcitation could all be identified and the degree of delay quantified. This overview will aim to establish the potential role of these new ultrasound methodologies in the recognition and quantitation of left-ventricular asynergy and how they might best be introduced into clinical practice.

Assessment of regional longitudinal myocardial strain rate derived from doppler myocardial imaging indexes in normal and infarcted myocardium.

Myocardial deformation properties may be characterized by regional strain rates (SRs) calculated from Doppler myocardial velocity data. In 10 control subjects and 12 patients with established transmural infarcts, longitudinal median segmental SR, strain, and myocardial velocity were analyzed and compared with the corresponding wall motion score. All segments in control subjects and normal segments in infarct patients showed no significant difference in either systolic or diastolic SR (systolic: -1.27+/-0.39 s(-1) versus -1.23+/-0.24 s(-1), not significant [NS]; and isovolumic relaxation [IVR]: 1.23+/-0.38 s(-1) versus 1.95+/-0.62 s(-1), NS; respectively) and strain (-0.21+/-0.06 versus -0.19+/-0.06, NS). In infarcted segments, peak systolic SR, systolic strain, and early diastolic SR showed the most pronounced reduction (hypokinetic and akinetic) or even inversion (dyskinetic segments: 0.10+/-0.26 s(-1), 0.00+/-0.03, and -1.78+/-0.67 s(-1), respectively; P<.001). In this study, new myocardial deformation indexes were shown to quantitatively describe the function of normal and chronically infarcted regions.

Normal regional right ventricular function and its change with age: a Doppler myocardial imaging study.

BACKGROUND: Doppler Myocardial Imaging (DMI) is a new technique currently being studied for the assessment of regional systolic and diastolic left ventricular (LV) function. No normal values or data on age-related changes in regional myocardial right ventricular (RV) velocities are available. METHODS AND RESULTS: Color DMI was used in 32 healthy volunteers (aged 16-76 years) to derive regional velocities from basal, medial, and apical segments of the RV free wall in the apical 4-chamber view, and from distal segments as well as from the tricuspid annulus in the parasternal long-axis view. Both mitral annular and regional LV velocities (4-chamber, long-axis parasternal view) were also recorded and compared with corresponding RV regional velocities. The M-mode displacement of the cardiac base was measured. Corresponding RV and LV DMI data sets were compared. For longitudinal function, RV free wall systolic velocities were consistently higher than velocities recorded in corresponding LV segments (analysis of variance, P <.05). Older subjects (40-76 years; 13 men, 2 women) had lower RV long-axis regional velocities than younger subjects (16-39 years; 15 men, 2 women), but had higher short-axis RV systolic velocities. For diastolic velocities, a negative correlation between age and the ratio of regional early diastolic to late diastolic velocity was shown for all RV free wall segments (eg, basal segment: r = -0.63, P <.0001). CONCLUSIONS: The right ventricle has higher long-axis regional velocities, a greater excursion of its lateral atrioventricular valve ring, and reduced circumferential shortening velocities compared with the left ventricle. Right ventricular longitudinal shortening is dominant over short-axis function in healthy young subjects. Normal age-related changes of diastolic velocities for each segment of the normal RV free wall have been defined.

Regional strain and strain rate measurements by cardiac ultrasound: principles, implementation and limitations.

The non-invasive quantification of regional myocardial function is an important goal in clinical cardiology. Myocardial thickening/thinning indices is one method of attempting to define regional myocardial function. A new ultrasonic method of quantifying regional deformation has been introduced based on the principles of 'strain' and 'strain rate' imaging. These new imaging modes introduce concepts derived from mechanical engineering which most echocardiographers are not familiar with. In order to maximally exploit these new techniques, an understanding of what they measure is indispensable. This paper will define each of these modalities in terms of physical principles and will give an introduction to the principles of data acquisition and processing required to implement ultrasonic strain and strain rate imaging. In addition, the current status of development of the technique and its limitations will be discussed, together with examples of potential clinical applications.

Abnormal postsystolic thickening in acutely ischemic myocardium during coronary angioplasty: a velocity, strain, and strain rate doppler myocardial imaging study.

We report a case in which the combination of gray scale imaging of wall thickness changes allied to color DMI regional velocity, strain, and strain rate data identified the development and regression of diastolic thickening in the acute ischemic segment during a right coronary artery percutaneous transluminal coronary angioplasty (PTCA). We also discuss the possible mechanisms and potential clinical implications of this finding.