Application of a simplified definition of diastolic function in severe sepsis and septic shock.

BACKGROUND: Left ventricular diastolic dysfunction is common in patients with severe sepsis or septic shock, but the best approach to categorization is unknown. We assessed the association of common measures of diastolic function with clinical outcomes and tested the utility of a simplified definition of diastolic dysfunction against the American Society of Echocardiography (ASE) 2009 definition. METHODS: In this prospective observational study, patients with severe sepsis or septic shock underwent transthoracic echocardiography within 24 h of onset of sepsis (median 4.3 h). We measured echocardiographic parameters of diastolic function and used random forest analysis to assess their association with clinical outcomes (28-day mortality and ICU-free days to day 28) and thereby suggest a simplified definition. We then compared patients categorized by the ASE 2009 definition and our simplified definition. RESULTS: We studied 167 patients. The ASE 2009 definition categorized only 35 % of patients. Random forest analysis demonstrated that the left atrial volume index and deceleration time, central to the ASE 2009 definition, were not associated with clinical outcomes. Our simplified definition used only e' and E/e', omitting the other measurements. The simplified definition categorized 87 % of patients. Patients categorized by either ASE 2009 or our novel definition had similar clinical outcomes. In both definitions, worsened diastolic function was associated with increased prevalence of ischemic heart disease, diabetes, and hypertension. CONCLUSIONS: A novel, simplified definition of diastolic dysfunction categorized more patients with sepsis than ASE 2009 definition. Patients categorized according to the simplified definition did not differ from patients categorized according to the ASE 2009 definition in respect to clinical outcome or comorbidities.

Association of left ventricular longitudinal strain with central venous oxygen saturation and serum lactate in patients with early severe sepsis and septic shock.

INTRODUCTION: In septic shock, assessment of cardiac function often relies on invasive central venous oxygen saturation (ScvO2). Ventricular strain is a non-invasive method of assessing ventricular wall deformation and may be a sensitive marker of heart function. We hypothesized that it may have a relationship with ScvO2 and lactate. METHODS: We prospectively performed transthoracic echocardiography in patients with severe sepsis or septic shock and measured (1) left ventricular longitudinal strain from a four-chamber view and (2) ScvO2. We excluded patients for whom image quality was inadequate or for whom ScvO2 values were unobtainable. We determined the association between strain and ScvO2 with logistic and linear regression, using covariates of mean arterial pressure, central venous pressure, and vasopressor dose. We determined the association between strain and lactate. We considered strain greater than -17% as abnormal and strain greater than -10% as severely abnormal. RESULTS: We studied 89 patients, 68 of whom had interpretable images. Of these patients, 42 had measurable ScvO2. Sixty percent of patients had abnormal strain, and 16% had severely abnormal strain. Strain is associated with low ScvO2 (linear coefficient -1.05, p =0.006; odds ratio 1.23 for ScvO2 <60%, p =0.016). Patients with severely abnormal strain had significantly lower ScvO2 (56.1% vs. 67.5%, p <0.01) and higher lactate (2.7 vs. 1.9 mmol/dl, p =0.04) than those who did not. Strain was significantly different between patients, based on a threshold ScvO2 of 60% (-13.7% vs. -17.2%, p =0.01) but not at 70% (-15.0% vs. -18.2%, p =0.08). CONCLUSIONS: Left ventricular strain is associated with low ScvO2 and hyperlactatemia. It may be a non-invasive surrogate for adequacy of oxygen delivery during early severe sepsis or septic shock.

Early Serial Echocardiographic and Ultrasonographic Findings in Critically Ill Patients With COVID-19.

Background: Cardiac function of critically ill patients with COVID-19 generally has been reported from clinically obtained data. Echocardiographic deformation imaging can identify ventricular dysfunction missed by traditional echocardiographic assessment. Research Question: What is the prevalence of ventricular dysfunction and what are its implications for the natural history of critical COVID-19? Study Design and Methods: This is a multicenter prospective cohort of critically ill patients with COVID-19. We performed serial echocardiography and lower extremity vascular ultrasound on hospitalization days 1, 3, and 8. We defined left ventricular (LV) dysfunction as the absolute value of longitudinal strain of < 17% or left ventricle ejection fraction (LVEF) of < 50%. Primary clinical outcome was inpatient survival. Results: We enrolled 110 patients. Thirty-nine (35.5%) died before hospital discharge. LV dysfunction was present at admission in 38 patients (34.5%) and in 21 patients (36.2%) on day 8 (P = .59). Median baseline LVEF was 62% (interquartile range [IQR], 52%-69%), whereas median absolute value of baseline LV strain was 16% (IQR, 14%-19%). Survivors and nonsurvivors did not differ statistically significantly with respect to day 1 LV strain (17.9% vs 14.4%; P = .12) or day 1 LVEF (60.5% vs 65%; P = .06). Nonsurvivors showed worse day 1 right ventricle (RV) strain than survivors (16.3% vs 21.2%; P = .04). Interpretation: Among patients with critical COVID-19, LV and RV dysfunction is common, frequently identified only through deformation imaging, and early (day 1) RV dysfunction may be associated with clinical outcome.

Right Ventricular Dysfunction in Early Sepsis and Septic Shock.

BACKGROUND: Sepsis is a frequently lethal state, commonly associated with left ventricular (LV) dysfunction. Right ventricular (RV) dysfunction in sepsis is less well understood. RESEARCH QUESTION: In septic patients, how common is RV dysfunction, and is it associated with worse outcomes? STUDY DESIGN AND METHODS: We measured echocardiographic parameters on critically ill patients with severe sepsis or septic shock within the first 24 hours of ICU admission. We defined RV dysfunction as fractional area change (FAC) less than 35% or tricuspid annulus systolic plane excursion (TAPSE) less than 1.6 cm. We defined LV systolic dysfunction as ejection fraction (EF) less than 45% or longitudinal strain greater than -19%. Using logistic regression, we assessed the relationship between 28-day mortality and presence of RV dysfunction and LV systolic dysfunction, controlling for receipt of vasopressors, receipt of fluid, mechanical ventilation, and the acute physiology and chronic health evaluation (APACHE II) score. RESULTS: We studied 393 patients. RV and LV dysfunction were common (48% and 63%, respectively). Mean echocardiographic values were: RV end-diastolic area, 22.4 ± 7.0 cm2; RV end-systolic area, 14.2 ± 6.0 cm2; RV FAC, 38 ± 11%; TAPSE, 1.8 ± .06 cm; RV longitudinal strain, -15.3 ± 6.5%; LV EF, 60% ± 14%; LV longitudinal strain, -16.5% ± 6.0%. Patients with RV dysfunction had higher 28-day mortality (31% vs 16%, P = .001). In our multivariable regression model, RV dysfunction was associated with increased mortality (OR, 3.4; CI, 1.7-6.8; P = .001), and LV systolic dysfunction was not (OR, 0.63; CI, 0.3 -1.2; P = .32) INTERPRETATION: Right ventricular dysfunction is present in nearly half of studied septic patients and is associated with over threefold higher 28-day mortality.

A simplified definition of diastolic function in sepsis, compared against standard definitions.

BACKGROUND: Guidelines for grading diastolic dysfunction poorly categorize septic patients. We compared how well the American Society of Echocardiography (ASE) 2009 and 2016 definitions and a simplified definition categorized septic patients. METHODS: We studied septic patients who received a transthoracic echocardiogram within 24 h of admission to an ICU. We categorized patients according to ASE 2009 and 2016 definitions and a definition using E/e', a surrogate for left ventricular filling pressure. We assessed 28-day all-cause mortality and the presence of pre-existing diabetes, hypertension, or myocardial infarction. We tested for associations among diastolic grade, comorbidities, and outcomes using logistic regression. RESULTS: We studied 398 patients. Mortality was 23%. The simplified definition categorized more patients than ASE 2016 (78% vs. 71%, p = 0.035); both definitions categorized more patients than ASE 2009 (34%, p < 0.001 for both comparisons). Higher grades of diastolic dysfunction were associated with hypertension (ASE 2016, simplified), myocardial infarction (ASE 2009, simplified), and diabetes (simplified). Grade of diastolic dysfunction was not associated with mortality by any definition. Of 199 patients categorized as normal by ASE 2016, 40% had an abnormal E/e' > 9 and 7% had a severely abnormal E/e' > 13. CONCLUSIONS: The ASE 2016 definition categorizes more septic patients than the ASE 2009 definition, but it does not categorize the diastolic function of a third of septic patients. ASE 2016 designates many patients with elevated E/e' as normal. A simplified definition categorized patients with less ambiguity and is associated with relevant comorbidities.

The peripheral blood transcriptome in septic cardiomyopathy: an observational, pilot study.

BACKGROUND: Septic cardiomyopathy (SCM) is common in sepsis and associated with increased morbidity and mortality. Left ventricular global longitudinal strain (LV GLS), measured by speckle tracking echocardiography, allows improved identification of impaired cardiac contractility. The peripheral blood transcriptome may be an important window into SCM pathophysiology. We therefore studied the peripheral blood transcriptome and LV GLS in a prospective cohort of patients with sepsis. RESULTS: In this single-center observational pilot study, we enrolled adult patients (age > 18) with sepsis within 48 h of admission to the ICU. SCM was defined as LV GLS > - 17% based on echocardiograms performed within 72 h of admission. We enrolled 27 patients, 24 of whom had high-quality RNA results; 18 (75%) of 24 had SCM. The group was 50% female and had a median (IQR) age of 59.5 (48.5-67.0) years and admission APACHE II score of 21.0 (16.0-32.3). Forty-six percent had septic shock. After filtering for low-expression and non-coding genes, 15,418 protein coding genes were expressed and 73 had significantly different expression between patients with vs. without SCM. In patients with SCM, 43 genes were upregulated and 30 were downregulated. Pathway analysis identified enrichment in type 1 interferon signaling (adjusted p < 10-5). CONCLUSIONS: In this hypothesis-generating study, SCM was associated with upregulation of genes in the type 1 interferon signaling pathway. Interferons are cytokines that stimulate the innate and adaptive immune response and are implicated in the early proinflammatory and delayed immunosuppression phases of sepsis. While type 1 interferons have not been implicated previously in SCM, interferon therapy (for viral hepatitis and Kaposi sarcoma) has been associated with reversible cardiomyopathy, perhaps suggesting a role for interferon signaling in SCM.

Associations among left ventricular systolic function, tachycardia, and cardiac preload in septic patients.

BACKGROUND: In sepsis, tachycardia may indicate low preload, adrenergic stimulation, or both. Adrenergic overstimulation is associated with septic cardiomyopathy. We sought to determine whether tachycardia was associated with left ventricular longitudinal strain, a measure of cardiac dysfunction. We hypothesized an association would primarily exist in patients with high preload. METHODS: We prospectively observed septic patients admitted to three study ICUs, who underwent early transthoracic echocardiography. We measured longitudinal strain using speckle tracking echocardiography and estimated preload status with an echocardiographic surrogate (E/e'). We assessed correlation between strain and heart rate in patients with low preload (E/e' < 8), intermediate preload (E/e' 8-14), and high preload (E/e' > 14), adjusting for disease severity and vasopressor dependence. RESULTS: We studied 452 patients, of whom 298 had both measurable strain and preload. Abnormal strain (defined as >-17%) was present in 54%. Patients with abnormal strain had higher heart rates (100 vs. 93 beat/min, p = 0.001). After adjusting for vasopressor dependence, disease severity, and cardiac preload, we observed an association between heart rate and longitudinal strain (ß = 0.05, p = 0.003). This association persisted among patients with high preload (ß = 0.07, p = 0.016) and in patients with shock (ß = 0.07, p = 0.01), but was absent in patients with low or intermediate preload and those not in shock. CONCLUSIONS: Tachycardia is associated with abnormal left ventricular strain in septic patients with high preload. This association was not apparent in patients with low or intermediate preload.