Myocardial Work in Septic Shock Patients (MYWORKSS)

Myocardial Work in Septic Shock Patients: an Observational Study

Myocardial strain analysis has emerged in the last decade as a reliable tool for studying myocardial mechanics, adding information on cardiac performance when compared with traditional parameters of left ventricle (LV) systolic function, such as ejection fraction (EF).

However, their relative load dependency makes the myocardial deformation indices unable to account for changes in pre- and afterload.

Myocardial work (MW) is emerging as an alternative tool for studying LV myocardial systolic function, because it incorporates both deformation and load into its analysis.

The purpose of this observational trial is to validate the use of MW in septic shock patients by means of consecutive echocardiographic assessment at predefined timepoints. Secondarily, we'll evaluate the impact of the vasoactive drugs used in septic shock patients (vasopressors and inotropes) on MW and on ventriculo-arterial coupling.

Study Overview

• Status: Not yet recruiting
• Conditions: Critical Illness; Septic Shock
• Intervention / Treatment: Device: Myocardial Work

Detailed Description

Myocardial strain analysis has emerged in the last decade as a reliable tool for studying myocardial mechanics, adding information on cardiac performance when compared with traditional parameters of left ventricle (LV) systolic function, such as ejection fraction (EF).

However, their relative load dependency makes the myocardial deformation indices unable to account for changes in pre- and afterload.

Myocardial work (MW) is emerging as an alternative tool for studying LV myocardial systolic function, because it incorporates both deformation and load into its analysis. In this context, MW could be considered as an advancement of myocardial strain, allowing to investigate LV performance also in cases of changes in afterload that could lead to misleading conclusions if relying only on strain analysis.

Conditions of increased afterload can in fact negatively impact on myocardial strain even if MWis normal. MW assessment was initially calculated using invasive pressure measurements, which limited its widespread use in clinical practice.

Recently, Russell et al. demonstrated that pressure-strain loops (PSLs) could estimate LV performance in a non-invasive manner, deriving LV pressure (LVP) curves from non-invasively acquired brachial artery cuff pressure. To date, the technique has been applied in myocardial ischaemia and in identification of cardiac resynchronization therapy (CRT)-responders with good results.

This clinical approach has been never tested, insofar, septic shock patients. The heart is one of the organs most frequently failing in sepsis; however, depending on the definition used, the prevalence of sepsis-induced cardiac dysfunction may vary between 10% and 70%. The sepsis-induced dysregulated inflammatory response has been directly linked to cardiomyocyte dysfunction, leading to a broad spectrum of cardiomyopathies, including ventricles' impairment during systole or diastole, inadequate cardiac output, oxygen delivery, or primary myocardial cellular injury.

Hence, in septic shocked patients, echocardiography plays a pivotal role, identifying most of the clinical cardiac patterns related to acute systolic dysfunction and chambers' dilation using basic level 2D and M-mode echocardiography. A more comprehensive diagnosis can be achieved with advanced levels of competency. Simultaneously, hemodynamic evaluation and monitoring are possible with advanced levels of competency, including the use of color Doppler, spectral Doppler, tissue Doppler imaging, and, eventually, 3D or speckled tracking. Specific pathways can now achieve all these steps of competence for skills certification, developed by intensive care medicine societies.

A variety of cardiac changes can be associated with septic shock, although a normal study is not unusual [7]. Abnormalities in LVEF (i.e., contractile impairment may be associated with either a global dysfunction or exhibited as specific patterns with apical akinesis and ballooning accompanied by good basal LV contraction and is almost always reversible over days), LV diastolic function, and right ventricular (RV) function have all been described. Since the resuscitation in septic shock is mainly focused on an aggressive and rapid fluid resuscitation associated with the administration of systemic vasopressors to optimize cardiac preload, output, and peripheral perfusion, the assessment of the basal cardiac function is critical and should be routinely performed at the bedside for this purpose.

The dynamic interaction between the heart and the systemic circulation allows the cardiovascular system to be efficient in providing adequate cardiac output and arterial pressures necessary for sufficient organ perfusion. The cardiovascular system provides adequate pressure and flow to the peripheral organs in different physiological and pathological conditions because of the continuous modulation of the arterial system compliance, stiffness and resistance with respect to LV systolic performance. This challenging interplay may lead to a condition called "ventriculo-arterial uncoupling", when the ration between myocardial performance and peripheral response (Ea/Ees) is unbalanced. The hemodynamic profile of septic shock is primarily characterized by generalized vasodilatation resulting in severe hypotension with systemic hypoperfusion. In most of the patients with septic shock, cardiovascular efficiency is impaired, and the Ea/Ees becomes uncoupled (Ea/Ees > 1). Th e hemodynamic profile is characterized by both the significant increase in Ea and the decrease in Ees. Because the increase in Ea is generally induced by pharmacological vasoconstriction. (norepinephrine) and the consequent increase in arterial tone, a decrease in Ees generally depends on the reduction in myocardial contractility. Whatever the underlying mechanism, when A-V uncoupling occurs in septic shock, the cardiac energetics are unfavorable and are often sacrificed to maintain tissue perfusion.

The purpose of this observational trial is to validate the use of MW in septic shock patients by means of consecutive echocardiographic assessment at predefined timepoints. Secondarily, we'll evaluate the impact of the vasoactive drugs used in septic shock patients (vasopressors and inotropes) on MW and on ventriculo-arterial coupling.

• Study Type: Observational
• Enrollment (Anticipated): 45

Contacts and Locations

• Study Contact: Name: Antonio Messina, PhD; Phone Number: 02-82241; Email: antonio.messina@humanitas.it

Study Locations

• Italy
  • Milan
    • Rozzano, Milan, Italy, 20089
      • Humanitas Clinical and Research center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with diagnosis of septic shock < 24h and acute circulatory failure was defined as at least one of the following criteria:

• Systolic arterial pressure ≤ 90 mmHg (or a decrease > 50 mm Hg in hypertensive patients) or a mean arterial pressure (MAP) ≤ 70 mmHg or the use of vasopressors to maintain SAP > 90 mmHg.
• skin mottling
• tachycardia ≥100 beats/min
• urinary flow ≤ 0.5 mL/kg for at least 2 hours
• blood lactate level ≥ 2 mmol/L.

Description

Inclusion criteria:

• Expected to be ventilated for > 48 hours
• Age > 50

Exclusion criteria:

• Atrial fibrillation (at the admission or during intensive care unit stay);
• Neuromuscular disorders;
• Home ventilation prior to admission;
• Palliative intubation;
• Intubation for an indication to tracheostomy;
• Poor acoustic window (after the first assessment);
• Severe mitral and/or aortic valve stenosis or regurgitation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Septic Shock Patients; Patients admitted with diagnosis of septic shock

Device: Myocardial Work; Myocardial work (MW) is emerging as an alternative tool for studying LV myocardial systolic function, because it incorporates both deformation and load into its analysis. In this context, MW could be considered as an advancement of myocardial strain, allowing to investigate LV performance also in cases of changes in afterload that could lead to misleading conclusions if relying only on strain analysis. This parameter will be evaluated by using an echographer equipped with a specific software for the analysis (Ecog Vivid E95 Ultra GE®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial Work	Quantification of Myocardial Work Index	24h from intensive care unit admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial Work	Quantification of Myocardial Work Index	60 +/- 12 h from intensive care unit admission
Myocardial Work	Quantification of Myocardial Work Index	7 days from intensive care unit admission

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial Work	Quantification of Myocardial Work Index	1h from norephinefrine infusion start
Myocardial Work	Quantification of Myocardial Work Index	1h from norephinefrine infusion dose increase
Myocardial Work	Quantification of Myocardial Work Index	6h from norephinefrine infusion dose increase
Myocardial Work	Quantification of Myocardial Work Index	1h from dobutamine infusion start

Collaborators and Investigators

• Sponsor: Humanitas Clinical and Research Center

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: December 3, 2021
• First Submitted That Met QC Criteria: December 3, 2021
• First Posted (Actual): December 15, 2021

Study Record Updates

• Last Update Posted (Actual): December 15, 2021
• Last Update Submitted That Met QC Criteria: December 3, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Shock, Septic; Shock; Critical Illness
• Other Study ID Numbers: MYWORKSS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No