In the crude regression model, longitudinal strain in patients with septic shock significantly worsened over 24 hours (P < 0.0001), whereas in patients with sepsis alone no change in longitudinal strain was observed over 24 hours (P = 0.43). No significant changes during the 24-hour measurement period were observed in either group for radial strain, circumferential strain, or ejection fraction (Table 3).
After multivariate adjustment for vasopressor administration and end-diastolic volume, the change in longitudinal strain observed over 24 hours in patients with septic shock persisted (P < 0.0001). Multivariate adjustment did not alter our findings of no change in radial strain, circumferential strain, or ejection fraction. In the sepsis group, no significant differences in longitudinal strain, radial strain, circumferential strain, or ejection fraction were noted after adjustment for end-diastolic volume.
After we stratified the groups for ischemic heart disease, our findings with respect to longitudinal strain did not change in either group (P = 0.44 for sepsis and 0.10 for septic shock). In addition, no significant differences in troponin between sepsis and septic shock patients were found at enrollment (P = 0.84) or at 24 hours (0.17).
As noted previously, no patients in the sepsis group received vasoconstrictors. Among all septic shock patients, 54.29% received only norepinephrine, 14.29% received only phenylephrine, and no patients received vasopressin only. In our study, 2 patients (5.7%) received both norepinephrine and phenylephrine, whereas 3 patients (8.6%) received both norepinephrine and vasopressin. The proportion of patients receiving norepinephrine, phenylephrine, and vasopressin simultaneously was 11.2%.
In this study of critically ill patients, speckle-tracking echocardiography identified worsening myocardial dysfunction over 24 hours in patients with septic shock but not sepsis alone. These changes were not detectable via echocardiographic measurement of ejection fraction but could be identified by assessment of myocardial strain. The time course of our findings also suggests that effects of septic shock on myocardial performance may occur early after the onset of shock. Targeting these patients early for intervention may improve outcomes.
Our study demonstrates the greater sensitivity of longitudinal strain as a measure of cardiac dysfunction in patients with septic shock and sepsis. After adjustment for vasopressor administration and end-diastolic volume, we found significant changes in longitudinal strain but saw no corresponding change in left ventricular ejection fraction over the same time period.
Our results are similar to previous animal and clinical studies in which authors compared strain echocardiography with ejection fraction measurement. Recently, Hestenes et al.16 demonstrated in a pig model a significant decrease in longitudinal strain without changes in ejection fraction (−17.2 ± 2.8 to −12.3% ± 3.2). Similar results in longitudinal strain were demonstrated by Basu et al.29 in a retrospective analysis of children admitted with septic shock.
Although left ventricular ejection fraction is used routinely for measuring left ventricular systolic function, newer techniques, such as speckle tracking, are increasingly used to monitor cardiac function in disease states, such as preeclampsia, cardiotoxic chemotherapy and Behcet disease.20,21,30 Although the mechanisms underlying changes in strain with septic shock are understood incompletely, one possibility is that microvascular vasoconstriction in the highly vulnerable subendocardial muscle layer might result in ischemic injury.31 Both coronary vasoconstriction and a decreased response to vasodilators, such as sodium nitroprusside in the coronary circulation, have been observed by Bogle et al.31 in a rabbit heart model of endotoxemia. This altered coronary microvascular tone may partly explain the changes in strain we observed.32 That we found changes in strain without corresponding changes in troponin levels suggests that strain identifies focal longitudinal muscle dysfunction rather than myocyte injury. Previous work suggests that the lack of change we observed in radial and circumferential strain represents compensation by the radial and circumferential fibers.33
Although factors affecting myocardial wall stress, such as afterload and volume status, may affect longitudinal or circumferential strain values,35–37 we observed differences in longitudinal strain even after adjustment for vasopressors. We also note that, despite using different vasopressor resuscitation strategies than Landesberg et al.,34 we report similar longitudinal strain values at 24 hours (−12.7 ± 5.64 vs −12.3 ± 3.6). Recent data in animals support the utility of strain measurement in the presence of vasopressors. In a rabbit model, Ho et al.36 found that at comparable blood pressures, strain did not depend on whether norepinephrine or phenylephrine was used or on the dose of vasopressin. In addition, changes in longitudinal strain are not significantly affected by positive end-expiratory pressure titration, which supports the validity of our data.38,39
Our study may have clinical implications. Once detected, subclinical myocardial dysfunction may be amenable to cardioprotective strategies, including β-blocker use, even if the ejection fraction remains normal. In one study of patients given cardiotoxic chemotherapy, β-blockers reversed changes in longitudinal strain.14 Another preliminary study in septic patients receiving norepinephrine found an improved outcome with β-blocker administration.8
Myocardial strain measurement may also help with prognosis in septic shock patients. Recently, Orde et al.40 demonstrated that, despite a normal ejection fraction, severe right ventricular free wall longitudinal strain dysfunction was associated with a high rate of mortality in patients with severe sepsis and septic shock.
Our observational study has limitations. Despite statistically significant differences, our sample size was small, which underscores the need for large-scale prospective studies to replicate our findings. In addition, our initial strain measurement was performed on admission to the ICU, not upon meeting septic shock or sepsis criteria. As a result, we cannot describe changes in longitudinal strain that occurred before or after our 24-hour monitoring period. We also did not measure strain during recovery from septic shock, to determine whether strain values regress to baseline values. Patients in the septic shock group also had a greater proportion of ischemic heart disease, which may have contributed to the changes that we found. Finally, speckle-tracking technology is relatively new, and current implementations require adequate endocardial border definition, which may be challenging because of volume resuscitation, mechanical ventilation, or suboptimal positioning. In addition, no standard values or protocols exist for strain analysis.
In summary, we conclude that early (<24-hour) changes in myocardial function because of septic shock are detectable using echocardiographic speckle-tracking technology. Our data raise the possibility that monitoring strain may better identify patients with myocardial dysfunction because of septic shock than measurement of ejection fraction. Whether early detection of subclinical left ventricular dysfunction and subsequent treatment can improve long-term outcome needs to be evaluated in future studies.
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