Myocardial Contrast Echocardiography in Septic Patients

Study of Myocardial Microcirculatory Alterations in Patients With Sepsis and Septic Shock Using Myocardial Contrast Echocardiography (MCE)

Myocardial microcirculatory alterations may be involved in the pathogenesis of acute cardiac dysfunction or septic cardiomyopathy in septic patients. The investigators study the cardiac function (systolic and diastolic) with two-dimensional echocardiography (TTE), and the myocardial microcirculation with contrast echocardiography (MCE) and sulphur hexafluoride microbubbles Sonovue injection in ICU septic patients.

Using the IE33 device (Philips Medical Systems, the Netherlands), two-dimensional and myocardial contrast echocardiography (TTE and MCE) are performed following the recommendations of the American Heart Association and the European Society of Cardiology (2006), and the European Association of Cardiovascular Imaging (2017). TTE and MCE are performed at the same time in the first 24 hours after ICU admission, at 48-72 hours, at 5-10 days after withdrawal of vasopressors and inotropes. First, TTE evaluates from the apical and parasternal views: The Wall motion score index (WMSI) of 16 myocardial segments of the left ventricle (LV). The diastolic function using pulsed-wave doppler and pulsed tissue doppler at the mitral valve. Quantify valvular insufficiency Estimation of cardiac output (L/ minute). Evaluation of the right ventricle (RV) dimension and its the longitudinal contractility by the Tricuspid annular plane systolic excursion (TAPSE) with pulsed tissue doppler. Left atrial volume (ml). Systolic pulmonary pressure and pulmonary resistance with both continuous and pulsed-wave doppler at the tricuspid valve and the pulmonary outflow tract, respectively. Second, MCE is performed if: Systolic blood pressure < 200 mmHg or > 90 mmHg, Heart rate < 130 or > 50 beats/minute Peripheral pulse oxygen saturation > 90% Arterial oxygen partial pressure (PaO2) ≥ 70 mmHg Arterial pH ≥ 7.25. Administration of contrast agent Sonovue requires an infusion pump (Vueject, Bracco, Milan, Italy), which provides constant agitation to maintain the homogeneity distribution of Sonovue. Injection of Sonovue allows an enhancement of LV endocardial border and regional function to evaluate: LV end-diastolic and end-systolic volumes (ml) and ejection fraction (%) using the Simpson method. The WMSI of the left ventricle (LV) after Sonovue injection. After optimization of transthoracic cardiac views, the mechanical index will settle between 0.1-0.2 and keeps unchanged during the procedure. Sonovue vial of 5 ml will dilute in in 10 ml saline solution and administrate at 0.7-1.5 ml/min. Using acquire flash-replenishment sequences during15 cardiac cycles of the apical 4-2-3 chamber views with the flash delivered after the second cardiac cycle. This technique destroys the microbubbles presents in the myocardium and allows replenishment with new microbubbles concentrations. The volume of blood within the entire coronary circulation at rest in diastole is predominantly resided within the capillaries. The myocardial signal intensity emanating from the contrast agent reflects the concentration of microbubbles within the myocardium. It takes 5 seconds for complete replenishment of the myocardium. Any decrease in myocardial blood flow prolongs replenishment time in proportion to its reduction. Immediately after microbubble infusion is started, all real-time MCE procedures are recorded for one minute and stored as DICOM (Digital Image Communications in Medicine) images. Offline analysis uses a specific quantification software named QLAB10 (Philips Medical Systems, the Netherlands) to convert myocardial perfusion images into time-intensity curves (TIC) corresponding to different regions of interest (ROI) of the 16 myocardial segments. Four variables are analyzed from these TIC curves to evaluate qualitatively the myocardial microcirculation: peak intensity (PI) in decibel (dB). time to peak intensity in seconds (TTP). mean transit time in seconds (MTT). Area under the curve in dB/seconds (AUC). The cardiac biomarkers including High sensivity cardiac troponin I for myocardial injury and N-terminal pro-brain natriuretic peptide (NT-proBNP) for heart failure are measured once daily in routine clinical practice.

Sepsis, Septic cardiomyopathy, Contrast echocardiography, Sulphur hexafluoride microbubbles contrast Sonovue

ICU patients with sepsis and septic shock who are eligible for myocardial contrast echocardiography with sulphur hexafluoride microbubbles contrast Sonovue (Bracco, Milan, Italy) injection.

Contrast myocardial echocardiography with sulphur hexafluoride microbubbles Sonovue (Bracco, Milan, Italy) injection and using the time-intensity curves profile to evaluate the myocardial microcirculation.

Qualitative evaluation of myocardial microcirculation using the variables of the time-intensity curve after Sonovue administration: The investigators hypothesize that patients who develop cardiac dysfunction will have a prolonged time to Peak intensity over time.

Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 to 72 hours, at 5 to 10 days after withdrawal of vasopressor and inotropic agents.

Qualitative evaluation of myocardial microcirculation using the variables of the time-intensity curve after Sonovue administration: The investigators hypothesize that patients who develop cardiac dysfunction will have a prolonged Mean transit time over time.

Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 to 72 hours, at 5 to 10 days after withdrawal of vasopressor and inotropic agents.

Qualitative evaluation of myocardial microcirculation using the variables of the time-intensity curve after Sonovue administration: The investigators hypothesize that patients who develop cardiac dysfunction will have a reduced Peak intensity over time

Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 to 72 hours, at 5 to 10 days after withdrawal of vasopressor and inotropic agents.

Qualitative evaluation of myocardial microcirculation using the variables of the time-intensity curve after Sonovue administration: The investigators hypothesize that patients who develop cardiac dysfunction will have a reduced Area under the curve (AUC) over time

Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 to 72 hours, at 5 to 10 days after withdrawal of vasopressor and inotropic agents.

Quantitative evaluation of the regional contractility of 16 myocardial segments of LV using the Wall motion score index. The investigators expect a lower score than 32 in patients who develop cardiac dysfunction over time

Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 to 72 hours, at 5 to 10 days after withdrawal of vasopressor and inotropic agents.

Quantitative evaluation of the global LV ejection fraction using the Simpson method. The investigators expect a lower ejection fraction than 50% in patients who develop cardiac dysfunction over time.

Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 to 72 hours, at 5 to 10 days after withdrawal of vasopressor and inotropic agents.

Mean change of the Tricuspid annular plane systolic excursion (TAPSE) of the right ventricle from baseline (mm)

Quantitative evaluation of the longitudinal contractility of the right ventricle by measuring the Tricuspid annular plane systolic excursion (TAPSE) with pulsed tissue doppler. The investigators expect lower values than 15 mm in patients who develop cardiac dysfunction over time.

Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 to 72 hours, at 5 to 10 days after withdrawal of vasopressor and inotropic agents.

Mean change of biomarker of cardiac injury: serum High sensitivity cardiac troponin I (micrograms/ L) from baseline.

Evaluation of the severity of myocardial injury associated with cardiac dysfunction by measuring High sensitivity cardiac troponin I. The investigators expect patients who develop cardiac dysfunction will have higher serum levels of this biomarker than those who do not over time.

Mean change of biomarker of heart failure: serum N-terminal pro-brain natriuretic peptide (NT-proBNP) (nanograms/ L) from baseline.

Evaluation of the degree of heart failure associated with cardiac dysfunction by measuring N-terminal pro-brain natriuretic peptide (NT-proBNP). The investigators expect patients who develop cardiac dysfunction will have higher serum levels of this biomarker than those who do not over time.

Inclusion Criteria: Sepsis: a life-threatening organ dysfunction (defined as an acute change in total Sequential Organ Failure Assessment (SOFA) score > 2 points consequent to infection) caused by a dysregulated host response to infection. Sepsis shock : a subset of sepsis with persisting hypotension requiring vasopressors to maintain the mean arterial pressure > 65 mmHg and having a serum lactate level > 2 mmol/L after fluid resuscitation. Exclusion Criteria: Non-survivors in the first 24 hours from sepsis Sepsis post-acute cardiac arrest Pregnancy Younger than 18 years old Acute Respiratory Distress Syndrome (ARDS) with the ratio of arterial oxygen partial pressure (mmHg) to fractional inspired oxygen (PaO2/ FiO2) < 200) Advanced malignancy Untreated and unstable acute coronary syndrome History of myocardial infarction with severe left ventricular dysfunction. (Ejection fraction < 20 %). Inoperable valvular and coronary disease Significant right-left cardiac shunt Untreated congenital heart disease Severe systolic pulmonary hypertension > 80 mmHg Insufficient echogenicity Prior anaphylaxis reaction to the Sonovue microbubbles

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