Pre-ejection mitral annular motion velocity responses to dobutamine infusion: A quantitative approach for assessment of myocardial viability

Abstract

Background

Dobutamine stress echocardiography (DSE) is widely used for detection of myocardial viability. The main limitation of DSE is its subjective interpretation. Assessment of mitral annular motion velocities with tissue Doppler imaging is a simple and quantitative measurement.

Objective

To determine the relationship between myocardial viability and regional systolic mitral annular motion tissue Doppler velocities responses to dobutamine stress.

Methods

Our study group included 42 patients with previous myocardial infarction referred for coronary angiography and revascularization. We did dobutamine stress tissue Doppler echocardiography (DSTDE) measuring velocities of pre-ejection wave (pre-Ej) and peak ejection wave (Ej) at rest and during low-dose dobutamine infusion. We did follow up echocardiography after 1 month.

Results

After exclusion of the normokinetic walls, we analyzed 196 walls. Using receiver operator characteristic ROC curves, the optimal cut-off value for viability assessment was an increase of 1.75 cm/s in pre-ejection velocity during DSTDE (area under the curve 0.70, p < 0.001). On the other hand, the optimal cut-off value for viability assessment was an increase of 1.75 cm/s in ejection velocity during DSTDE (area under the curve 0.613, p = 0.01). The sensitivity, specificity, and total accuracy of the DSTSE (pre-Ej) versus the gold standard for detection of myocardial viability were 66.15%, 67.94%, and 67.35%, respectively. The sensitivity, specificity, and total accuracy of the DTSE (Ej) were 56.92%, 64.12%, and 61.43%, respectively. There was a good correlation between the pre-Ej at 5 ug/kg/min dobutamine infusion and the pre-Ej after revascularization (r = 0.64, p = 0.01) while the correlation with the Ej was moderate (r = 0.50, p = 0.01).

Conclusion

Viable left ventricular myocardium could be identified easily and quantitatively with pre-ejection mitral annular velocity during dobutamine infusion. The pre-ejection wave during DSTDE showed greater sensitivity and specificity for the prediction of myocardial viability than the ejection wave.

Abbreviations

+Vic

myocardial positive pre-ejection velocity

CABG

Gcoronary artery bypass grafting

CI

95% confidence interval

DSE

Dobutamine stress echocardiography

DSTDE

dobutamine stress tissue Doppler echocardiography

EF

ejection fraction

Ej

ejection wave

IVS

interventricular septal thickening

LA

left atrial diameter

LAD

left anterior descending

LCX

left circumflex

LDDSE

low dose dobutamine stress echocardiography

LV

left ventricular

LVEDD

left ventricular end diastolic diameter

LVEF

left ventricular ejection fraction

LVESD

left ventricular end systolic diameter

MI

myocardial infarction

MRI

magnetic resonance imaging

PCI

percutaneous coronary intervention

PET

positron emission tomography

pre-Ej

pre-ejection wave

PW

posterior wall thickening

RCA

right coronary artery

ROC

receiver operator characteristic

TDI

tissue Doppler imaging

Introduction

Assessment of myocardial viability in patients with myocardial infarction is important. Myocardial scintigraphy [1], dobutamine stress echocardiography, [2] and contrast echocardiography [3] are used in the determination of viability. Among these procedures, dobutamine stress echocardiography is widely used in the clinical setting because it is a safe and accurate method for detection of myocardial viability. The main limitation of dobutamine echocardiography is its subjective interpretation [4].

Because the mitral annulus shifts towards the cardiac apex during systole [5], the mitral annular motion recorded with M-mode echocardiography correlates with the left ventricular ejection fraction [6,7] and myocardial viability [8]. One study showed that changes in the amplitude of the AV plane displacement during low-dose dobutamine stress echocardiography can easily be used to detect myocardial viability at an early stage with late potential for spontaneous recovery [9].

Tissue Doppler imaging facilitates the direct measurement of the left ventricular wall and mitral annular motion velocities [10,11]. This method can therefore be used for quantitation of regional left ventricular wall motion [12]. Thus, the parameters obtained from mitral annular systolic motion velocities with pulsed tissue Doppler imaging reflect left ventricular (LV) asynergy corresponding to the infarct regions in patients with myocardial infarction, and global LV systolic function may be evaluated with these parameters [13]. Assessment of mitral annular motion velocities along the long axis with tissue Doppler imaging has several advantages over other methods, such as the simplicity of measurement, superior time resolution, and preload independence [13–15].

However, there have been no many studies correlating myocardial viability and regional systolic mitral annular motion velocity response to dobutamine stress, particularly during early systole. It has been found that the pre-systolic annular motion towards the cardiac apex accurately predicts regional left ventricular myocardial viability [12].

Objective

The objective of this study is to determine the accuracy of regional systolic mitral annular motion tissue Doppler velocities responses to dobutamine stress in the detection of myocardial viability in patients with previous myocardial infarction.

Methodology

We enrolled consecutive patients with previous myocardial infarction who were referred to Ain Shams University Hospitals for coronary angiography and revascularization.

Inclusion criteria were: (1) Significant (>50%) reduction in the luminal diameter of a major coronary artery corresponding to the infarcted area on the basis of recent coronary angiographic results; (2) previous Q-wave myocardial infarction of more than one-week duration; and (3) regional left ventricular wall motion abnormality corresponding to the infracted region on the basis of two-dimensional echocardiography. The infract-related coronary artery stenosis was revascularized by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).

Exclusion criteria were: (1) Postinfarction unstable angina or infarction complicated by severe hemodynamic instability; (2) decompensated congestive heart failure; (3) protruding thrombus in the left ventricular cavity with fresh mobile edges; (4) significant valvular or congenital heart disease; (5) any myocardial disease apart from ischemia; (6) coexistent relevant liver or renal disease; (7) a contraindication to dobutamine administration particularly; (8) moderate or severe mitral regurgitation; and (9) technically inadequate echocardiographic imaging.

The study was approved by the medical ethics committee of our institution. The study protocol was designed in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans. All patients gave informed consent before the procedure.

Baseline transthoracic echocardiographic examination: Images were acquired with the patient in the left lateral decubitus position using a multifrequency phased array transducer of 2.5–3.5 MHz attached to Vivid V echocardiography machine (General Electric medical systems, manufactured in Horten, Norway) equipped with Doppler tissue imaging (DTI) technology. We measured the left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left atrial diameter (LA), Ejection fraction (EF), resting segmental wall motion. The left ventricle was divided into the standard 16-segment model recommended by the American Society of Echocardiography [16]

We graded each myocardial segment using the following semi-quantitative scoring system: Normal contraction was defined as 5 mm endocardial excursion, 25% systolic thickening, and assigned a score of 1. Hypokinesia was defined as <5 mm endocardial excursion, <25% systolic thickening, and assigned a score of 2. Akinesia was defined as virtual absence of systolic myocardial thickening, even if slight inward motion was present during systole, and assigned a score of 3. Dyskinesia was defined as paradoxical endocardial excursion away from the left ventricular lumen in systole, and assigned a score of 4.

Aneurysm was defined as continuous distortion of the wall both in systole and diastole, and assigned a score of 5. Aneurysm with scar was defined as score 5 + scar of previous MI. It was assigned a score of 6.

Dobutamine stress tissue Doppler echocardiography (DSTDE)

We infused dobutamine in a stepwise manner (0, 5 and 10 ug/kg/min) during 3 min intervals. At each dose, heart rate and blood pressure were measured. We calculated left ventricular ejection (LVEF) fraction at rest and at the end of each infusion stage of the pharmacologic stress protocol.

DSTDE was done for studying the systolic mitral annular motion velocities at six mitral annular sites that reflect the asynergy at these sites corresponding to the infarct regions in patients with myocardial infarction: (anteroseptal and posterior walls in the apical long axis view, posteroseptal and lateral walls in the apical 4-chamber view, and anterior and inferior walls in the apical 2-chamber view). The acoustic power and filter frequencies of the ultrasound scan system were set to the lowest values possible, and the sample columns (width of approximately 8 mm) were set at the mitral annulus. The peak velocity was determined as the average peak velocity from three consecutive beats, both in the pre-ejection phase and during left ventricular contraction in the ejection period. Briefly, to define the pre-ejection period, aortic flow was recorded by pulsed-wave Doppler at the level of LV outflow tract at the beginning and at the end of each examination. Pre-ejection was defined as a time interval between the onset of QRS complex and the onset of aortic flow. Cardiac cycles with extrasystolic, post-extrasystolic beats, or any rhythm disturbance were excluded. Recording was repeated during dobutamine infusion at 0, 5 and 10 ug/kg/min. Analysis was performed by one observer (AO). Measurements of theses parameters were highly reproducible by the same observer for each patient. Reproducibility (intra-observer variability) was assessed by coefficient of variation for repeated measures in the first 10 patients.

End points for interrupting any of the above mentioned infusion protocols were: (1) intolerable symptoms such as severe headache, severe nausea and vomiting; (2) severe chest pain and/or dyspnea with evidence of clinical ischemia defined as ⩾2.0 mm of additional ST segment depression or elevation in at least two contiguous leads compared with rest ± new remote wall motion abnormality or worsening contractility in previously asynergic segments; (3) limiting asymptomatic side effects including hypertension (systolic blood pressure > 220 mmHg and/or diastolic blood pressure > 120 mmHg), hypotension (relative or absolute i.e. >30 mmHg decrease in blood pressure), sustained supraventricular tachyarrhythmia particularly atrial fibrillation, ventricular arrhythmias (frequent, polymorphous premature ventricular beats or ventricular tachycardia) and bradyarrhythmias. In the event of demonstrable ischemia, intravenous beta blockers and/or nitroglycerin were administered.

Follow up

We performed transthoracic two-dimensional echocardiography at 1 month after revascularization to detect improvement in regional wall motion and left ventricular function. Also, another TDI study was conducted during follow-up to detect improvement in the value of the pre-ejection wave or ejection waves. Improvement after revascularization (the gold standard of viability) was considered if there was any improvement by one or more grades of at least one myocardial segment of the affected wall.

Statistical analysis

The data were statistically analyzed using the Statistical Package for Social Sciences (SPSS) software version 14. Categorical variables were compared by Chi square test. Continuous normally distributed variables were compared by Paired-sample t-test. Pearson correlation was done for continuous variables. Specificity and sensitivity of dobutamine mitral annular TDI echo were calculated against the gold standard of viability (improvement with revascularization). The optimal pre-ejection and ejection velocity changes for the prediction of myocardial viability (improvement with revascularization) were determined by a receiver operator characteristic (ROC) curve constructed for the pre-ejection and ejection velocity values. A p value ⩽0.05 (2-tailed) was considered significant and a p value ⩽0.01 was considered highly significant.

Results

The study included 42 consecutive patients with recent or old myocardial infarction with documented significant coronary artery disease by coronary angiography and submitted to elective percutaneous coronary intervention (18 patients) or coronary artery bypass grafting surgery with two or three grafts (24 patients). They all underwent complete successful revascularization that included the infarct-related arteries. The baseline characteristics are detailed in Table 1.

Table 1.

Baseline clinical and angiographic characteristics of the study group.

	Patients (n = 42)
Age in years	53.5 ± 8.7
Sex
Male	38 (90.5%)
Female	4 (9.5%)
Risk factors
Smoking	33 (78.6%)
Diabetes	15 (35.7%)
Hypertension	16 (38.1%)
Dyslipidemia	15 (35.7%)
Family history	9(21.4%)
Previous MI
Anterior	24 (57.1%)
Inferior	5 (11.9
Anterior and inferior	13 (31%)
Duration of MI in months	7.3 ± 11.3
Coronary artery affection
LAD	38 (90.5%)
LCX	31 (73.8%)
RCA	26 (21.9%)
Coronary artery affection
Single vessel	9 (21.4%)
Double vessel	13 (31%)
Three vessel	20 (47.6%)
Baseline echocardiography
LVEDD in mm	59.8 ± 9.2
LVESD in mm	45.4 ± 9.7
IVS in mm	9.7 ± 1.6
PW in mm	1.3 ± 1.3
LVEF	38.2 ± 9.5
LAD in mm	39.4 ± 7.1

MI = myocardial infarction, LAD = left anterior descending, LCX = left circumflex, RCA = right coronary artery, LVEDD = left ventricular end diastolic diameter, LVESD = left ventricular end systolic diameter, IVS = interventricular septal thickening, PW = posterior wall thickening, LVEF = left ventricular ejection fraction, LAD = left atrial diameter. Data are expressed as a mean ± standard deviation or a number (percent).

The LVEF at rest was 38.2 ± 9.5% while at 5 ug/kg/min infusion rate of dobutamine during the study was 43.2 ± 9.7%. The ejection fraction improved at one-month follow up after revascularization (38.2 ± 9.5% vs. 44.1 ± 10.3%, p = 0.0001). There was an excellent correlation between LVEF during 5 ug/kg/min dobutamine infusion and LVEF after revascularization (r = 0.93, p < 0.0001).

Detection of myocardial viability

Low dose dobutamine echocardiography for detection of viability was performed on the 42 patients by using TDI. Among the 42 patients, 252 walls were studied. The normokinetic walls at rest detected by 2D conventional echocardiography were excluded from the study, so the remaining diseased walls were 196. Table 2 presents the values of the pre-ejection and the ejection waves during DSTDE. Both waves increased significantly during dobutamine infusion (5 ug/kg/min).

Table 2.

Mitral annular tissue Doppler pre-ejection and ejection velocities during DSTDE.

Velocities (cm/s)	Rest	Dobutamine (5 ug/kg/min)	p Values
Pre-ejection wave	5.86 ± 1.69	7.59 ± 2.32	0.001
Ejection wave	7.47 ± 1.59	9.23 ± 2.01	0.001

Data expressed as mean ± standard deviation.

Another two-dimensional and TDI study was conducted after revascularization at one-month follow up. Improvement was detected at one-month post-revascularization in 65 walls out of the 196 walls (33.16%).

There was good correlation between the pre-ejection wave at 5 ug/kg/min dobutamine infusion and the pre-ejection wave after revascularization (r = 0.64, p = 0.01). There was moderate correlation between the ejection wave at 5 ug/kg/min dobutamine infusion and the ejection wave after revascularization (r = 0.50, p = 0.01).

Using ROC curves, the optimal cut-off value for viability assessment was an increase of 1.75 cm/s in pre-ejection velocity during DSTDE (65% sensitivity, 67% specificity, area under the curve 0.70, p < 0.001, Fig. 1). On the other hand, the optimal cut-off value for viability assessment was an increase of 1.75 cm/s in ejection velocity during DSTDE (58% sensitivity, 63% specificity, area under the curve 0.613, p = 0. 01, Fig. 2).

Figure 1.

ROC curve: the best cut-off value for the change of the pre-ejection wave at 5 ug/kg/min dobutamine infusion to predict improvement after revascularization is 1.75 cm/s. AUC = 0.700, CI = 0.627–0.773, p = 0.001.

Figure 2.

ROC curve: THE best cut-off value for the change of the ejection wave at 5 ug/kg/min dobutamine infusion to predict improvement after revascularization is 1.75 cm/s. AUC = 0.615, CI = 0.533–0.693, p = 0.01.

The diagnostic accuracy of the DSTDE was calculated against the gold standard of viability (improvement after revascularization). DSTDE (pre-ejection wave) correctly identified 43 walls as viable and 89 walls as non-viable. Twenty-two walls were erroneously classified as non-viable and 42 walls as viable. Thus, the sensitivity, specificity, and total accuracy of the DSTDE (pre-ejection wave) were 66.15%, 67.94%, and 67.35%, respectively.

DSTDE (ejection wave) correctly identified 37 walls as viable and 84 walls as non-viable. Twenty-eight walls were erroneously classified as non-viable and 47 walls as viable. Thus, the sensitivity, specificity, and total accuracy of the DSTDE (ejection wave) were 56.92%, 64.12%, and 61.43%, respectively (Table 3).

Table 3.

The diagnostic accuracy of the DSTDE.

	DSTDE (pre-ejection wave)	DSTDE (ejection wave)
Sensitivity	66.15% CI: 53.35–77.43%	56.92%CI: 44.04–69.15%
Specificity	67.94% CI: 59.22–75.82%	64.12% CI: 55.28–72.31%
Positive predictive value	50.59% CI: 39.52–61.61%	44.05% CI: 33.22–55.30%
Negative predictive value	80.18% CI: 71.54–87.14%	75.00% CI: 65.93–82.70%

DTSE = dobutamine stress tissue Doppler echocardiography, CI = 95% confidence interval.

Discussion

Assessment of myocardial viability in patients with myocardial infarction is important. Dobutamine stress echocardiography is widely used in the clinical setting because it is a safe and accurate method for detection of myocardial viability. The main limitation of dobutamine echocardiography is its subjective interpretation [4]. TDI, as a quantitative technique for the assessment of myocardial velocities, is at least as accurate in identifying viable myocardium as are traditional qualitative methods. However, the recording of myocardial velocities during the dobutamine stress echo is a time consuming technique [17–18]. The need to acquire all values on-line within a limited time margin at peak stress is a limitation of this modality [18].

Assessment of mitral annular motion velocities along the long axis with tissue Doppler imaging has several advantages over regional left ventricular wall motion velocities, such as the simplicity of measurement, superior time resolution, and preload independence [13–15]. Various studies have focused on the relationship between mitral annular motion and LV systolic function. Specifically, it has been reported that mitral annular motion determined with M-mode or two-dimensional echocardiography correlates with the LVEF in healthy individuals or in patients with heart diseases [6,7]. Alam found that the amplitude of mitral annular motion decreases in infracted regions [7]. In addition, another study reported that systolic mitral annular motion toward the cardiac apex measured with M-mode echocardiography could have a high degree of sensitivity and specificity for detection of myocardial viability [8]. It was also found that the correlation between ejection fraction (EF) and the systolic mitral annular velocity is relatively good irrespective of the presence or absence of significant mitral regurgitation. Measurements of annular velocities constitute a simple and useful method for evaluating patients with heart failure [19]. In another study, it was found that M-mode echocardiography and pulsed-wave DTI used for assessment of mitral annular motion are useful methods for evaluation of LV function. However, parameters measured by pulsed-wave DTI correlate more strongly with plasma brain natriuretic peptide levels than those measured by M-mode echocardiography and provide a simple, sensitive, accurate and reproducible tool for early diagnosis of LV dysfunction [20].

Therefore, the main point of this study was that TDI of the mitral annular motion, as a quantitative and easy technique for the assessment of myocardial viability, is accurate in identifying viable myocardium in patients with previous myocardial infarction.

These results coincide with those of an earlier report which also studied the response of systolic mitral annular motion velocities to dobutamine infusions and its relation to prediction of myocardial viability. The study included 45 patients with previous myocardial infarction. A 99mTc-methoxyisobutylisonitrile scintigraphy was performed to detect viability. This study showed that when the cut-off value for an increase in pre-systolic wave was set at 2 cm/s, myocardial viability was predicted with a sensitivity of 92% and specificity of 90% [12]. When the cut-off value for an increase in systolic wave was set at 2 cm/s, myocardial viability was predicted with a sensitivity of 67% and specificity of 58% [12].

Another report investigated low dose dobutamine stress echocardiography (LDDSE) combined with tissue Doppler imaging (TDI) of the myocardial segments for the quantitative assessment of the content of viable myocardium (defined according to postoperative recovery) [18]. Conventional qualitative LDDSE showed a sensitivity of 78% and specificity of 85% in predicting myocardial recovery. The optimal cut-off value for viability assessment was an increase of 0.5 cm/s in ejection velocity during LDDSE (80% sensitivity and 88% specificity, area under the curve 0.801), 0.6 cm/s in pre-ejection velocity (91% sensitivity and 90% specificity, area under the curve 0.890) [18].

Penicka et al. [21] assessed the accuracy of tissue Doppler imaging-derived myocardial positive pre-ejection velocity (+Vic) in detecting myocardial viability defined by dobutamine stress echocardiography (DSE), fluorine-18 fluorodeoxyglucose positron emission tomography (PET), contrast-enhanced magnetic resonance imaging (MRI), and recovery of left ventricular (LV) function after coronary artery bypass grafting in patients with chronic ischemic LV dysfunction. A good agreement was observed between +Vic and detection of viable myocardium at DSE, PET, and MRI (kappa = 0.76). The presence of +Vic in greater than or equal to five dysfunctional segments had the highest sensitivity (93%) and specificity (60%) to identify patients (n = 28) with > or =10% increase in LVEF between baseline and six-month echocardiogram [21].

Another study tested the ability of pre-ejection velocity to predict recovery of myocardial contractile function after coronary revascularization in acute myocardial infarction. Longitudinal myocardial velocities were recorded at rest by pulsed-wave TDI echocardiography 6 +/− 2 h after revascularization. They showed a positive pre-ejection velocity after revascularization predicted recovery of contractile function in the reperfused area [22].

Thus, several studies found that when myocardial viability was evaluated by TDI, the pre-ejection wave during early systole showed greater sensitivity and specificity for the prediction of myocardial viability than the ejection wave. It has been reported that endocardial dysfunction generally occurs during the early stages of ischemia, resulting in a predominant impairment of longitudinal fiber contraction during early systole [23,24]. Residual viability of longitudinal fibers in the infarcted region is closely associated with an increase in pre-ejection wave velocity after dobutamine administration [12]. Moreover, segments with extensive scar tissue may show an increase in ejection velocity during dobutamine infusion due to the tethering effect of adjacent viable myocardium. A possible way to avoid this effect could be the evaluation of pre-ejection velocity changes. During that period, the left ventricle does not change its shape, and the tethering effect is thus minimized. Furthermore, the effect of cardiac rotation is lower during the pre-systolic period than during the ejection period.

The increase in wall thickness that occurs in normal myocardium after ventricular activation and before aortic opening corresponds to the brief pre-ejection velocity. In our study, the pre-ejection velocity increased during low dose dobutamine infusion. There was good correlation between the pre-ejection wave at 5ug/kg/min dobutamine infusion and the pre-ejection wave after revascularization (r = 0.64, p = 0.01). This means that viable hibernating myocardium may contract at rest when both left ventricular pressure and wall stress are low (e.g. during pre-ejection phase); however, it cannot sustain the higher load during ejection. This is consistent with findings that positive pre-ejection velocity wave is a sign of non-transmural necrosis [25] and that increased segmental systolic velocity during low dose DSE is associated with viability of these segments [26].

Therefore, the pre-ejection wave more sensitively reflects myocardial viability than the ejection wave and gives important information for the detection of reversible myocardial dysfunction (hibernation) with low dose dobutamine stress. Furthermore, because pulsed TDI facilitates the evaluation of myocardial viability along the long axis, measurements are relatively easier to evaluate than measurements along the short axis, and are minimally influenced by whole heart motion. To the best of our knowledge, our study is the first study to predict myocardial viability, defined by improvement after revascularization, with pre-ejection mitral annular velocity during dobutamine stress tissue Doppler echocardiography.

Currently, the most cost-effective imaging techniques to detect reversible contractile function are stress echocardiography and nuclear perfusion imaging [1,2]. Echocardiography has the advantage of widespread availability, but subjective evaluation remains its main limitation [4]. TDI provides quantitative data; however, the recording of myocardial velocities during dobutamine stress echo is a time consuming technique [18]. Therefore, recording of mitral annular TDI velocities is relatively simple and should be technically feasible for evaluation of regional myocardial viability in patients with myocardial infarction.

Limitations of the study

We arbitrarily timed the outcome of dysfunctional segment 1 month after revascularization to avoid the interaction of possible restenosis on functional recovery. However, potential functional improvement after this time cannot be ruled out. Accurate definition of culprit artery restenosis could have been done with another follow-up angiography, but that would have increased the cost of the study. Pulsed TDI was performed at the level of the mitral annulus, but the regional myocardium itself was not evaluated. Therefore, measured values might be influenced by the infarcted area or wall motion in the non-infarcted regions. Moreover, left atrial hemodynamics might influence mitral annular motion in patients with markedly elevated LV end diastolic pressure or left atrial dilatation. It was not possible to assess the ability of TDI to optimize prediction of death-free outcome in long-term follow-up.

Conclusion and recommendations

Viable left ventricular myocardium could be identified quantitatively and easily with peak pre-ejection mitral annular velocity during dobutamine stress tissue Doppler echocardiography. The pre-ejection wave during early systole showed greater sensitivity and specificity for the prediction of myocardial viability than the ejection wave. In view of the small sample size included in this report, larger clinical studies are needed to confirm these observations.

Appendix A. Supplementary data

Supplementary Figure 1.

Showing pulsed wave-TDI recording of the anterior septum in case no. 35 at rest. The pre-ejection wave value was 4.7 cm/s at rest.

Supplementary Figure 2.

Showing pulsed wave-TDI recording of the anterior septum in case no. 35 during dobutamine infusion at a rate of 10 ug/kg/min. The pre-ejection wave value was 10.0 cm/s at 5 ug/kg/min dobutamine infusion then increased to 12.14 cm/s at 10 ug/kg/min dobutamine infusion.

Supplementary Figure 3.

Showing pulsed wave-TDI recording of the anterior septum in case no. 35 at rest at follow up. The pre-ejection wave value was 5.7 cm/s.