REVIEW | Effect of Intermittent High–Mechanical Index Impulses on Left Ventricular Strain

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REVIEW | Effect of Intermittent High–Mechanical Index Impulses on Left Ventricular Strain

Source: JASE 2021;34(4):370-376


Endocardial border resolution can be improved by using Intermittent high–mechanical index (MI) impulses during ultrasound enhancing agent (UEA) infusion. In animal models, these high-MI impulses have been shown to also release adenosine triphosphate (ATP) for sustained periods of time.

Since contractility is highly dependent on the concentration of high-energy phosphates released with ATP hydrolysis, it is reasonable to assume that the cavitation created by transthoracic high-MI impulses during contrast infusion has an effect on myocardial contractility.

The purpose of this study was to evaluate if the cavitation created during impulses during contrast infusion has an effect on global longitudinal strain (GLS) – a measure of left ventricular systolic function.


This randomized prospective trial was taken among 50 patients referred to the echocardiography laboratory for evaluation of different symptoms:

  • Chest pain evaluation – 14
  • Pre- or postoperative evaluation of LV systolic function – 13
  • Congestive heart failure – 11
  • Paroxysmal atrial fibrillation – 2
  • Unexplained shortness of breath – 4
  • Hypertension – 3
  • Evaluation of aortic valve disease – 3

Patients were prospectively randomized to very low MI (VLMI) imaging only, versus VLMI imaging with intermittent high-MI impulses during resting contrast echocardiography. Baseline tissue harmonic imaging (1.7 MHz, MI = 1.1, 67 Hz) was performed in the apical four, two, and three-chamber windows for analysis of GLS.

Patients underwent continuous infusion of a 5% Definity (Lantheus Medical Imaging, North Billerica, MA), and baseline myocardial contrast-enhanced images were obtained using VLMI imaging (power modulation) using an MI of 0.18 and a center frequency of 1.8 MHz.

Patients randomized to VLMI imaging alone had power modulation imaging at an MI of 0.18 without any high-MI impulses. Patients randomized to intermittent high-MI imaging received at least two high-MI impulses (MI = 1.0-1.2, five frames, 1.8 MHz) in each of the three apical windows.

The contrast infusion was terminated after all apical and parasternal views had been obtained. Patients then underwent repeat imaging at 5-min intervals for up to 10 min after cessation of the contrast infusion for GLS measurements using the same settings as at baseline. At these time points after contrast infusion, there was minimal or no evidence of residual contrast within the LV cavity or myocardium. On the basis of biplane enhanced LV volume measurements at end-diastole and end-systole, patients were classified as having a normal or abnormal resting LVEF using a cutoff of 50%.


There were no differences in any demographic variable between groups. In 19 patients (38%), baseline LVEF was <50% and not different proportionally between groups. Similarly, LVEF, cavity dimensions, and transmitral E/e’ ratio were similar between groups. 

GLS Measurements before and after Imaging Protocols

There were no differences in heart rate or mean arterial pressure between group 1 and group 2. GLS measurements in group 1 patients undergoing VLMI imaging alone were not different at either the 5- or 10min time point following contrast infusion (P < .0001 at both time points after contrast infusion). In contrast, group 2 patients had increases in GLS at these same 5- and 10-min time points. This increase in strain in group 2 patients was seen when systolic function was both normal and abnormal. Ten of 15 patients in group 2 (67%) with normal LVEFs had absolute increases in GLS of $1% at 10 min after contrast infusion compared with none of the patients in group 1 (P < .0001).


The authors pointed out that this was the first study to document at least a transient biologic effect on systolic function in humans of intermittent high-MI impulses applied during infusion of a commercially available contrast agent. The improvement in GLS was variable but was related to the effect of the intermittent high-MI impulses. This temporary effect on LV systolic function in patients with both normal and abnormal ejection fractions.