Diastolic Dysfunction in Septic Shock and Cardiomyopathy Genetic Variants

NCT05552521 | Completed

• 1 other identifier: TI 01/2022
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is a life-threatening infection with increasing incidence, and its spectrum of disease can involve cardiac dysfunction, which further adds to mortality. Although cardiac involvement in sepsis has been classically attributed to systolic dysfunction, diastolic dysfunction is increasingly diagnosed due to new echocardiographic techniques and the conceptual evolution of diastolic dysfunction. Combining systolic and diastolic dysfunction assessment could lead to a better diagnosis of septic cardiac dysfunction. Furthermore, earlier forms of septic cardiac dysfunction could be more promptly recognized by measuring novel and less used parameters of diastolic dysfunction. We hypothesize that left atrium (LA) strain and isovolumetric relaxation time (IVRT) derived intervals could be new and earlier predictors of diastolic dysfunction in septic patients with a potential impact on clinical presentation and prognosis and that rare genetic variation associated with inherited cardiomyopathies could underline the risk and severity of sepsis-related myocardial dysfunction with potential impact on diagnosis and prognosis.

Conditions

Diastolic Dysfunction; Septic Shock; Cardiomyopathies

Outcome Measures

Primary Outcomes (2)

• Diastolic dysfunction

  Left atrium strain in % and IVRTs intervals in msec

  through study completion until 6 months

• Hereditary Cardiomyopathy genetic variants

  Search for cardiomyopathies genetic variantes that could explain a myocardial susceptibility to develop injury in septic shock

  through study completion until 6 months

Secondary Outcomes (2)

• Heart failure

  through study completion until 6 months

• Mortality

  through study completion until 6 months

Interventions

Echocardiography DIAGNOSTIC_TEST

Echocardiography in 4 timepoints: 1st 24h + 7th-10th day; 28th-30th day; 6 months Whole exome sequencing at admission

Also known as: Genetic analysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

A prospective multicenter observational study in the 30-bed polyvalent ICU of Hospital Garcia de Orta, Almada, Portugal. Expected sample size of 140 patients, to have a confidence level of 95%, with a precision within ± 5% (population of septic patients in the ICU/yearly).

You may qualify if:

• All patients admitted in the ICU i. ≥ 18 years old; ii. with septic shock by the sepsis 3.0 criteria (13): Sepsis and (despite adequate volume resuscitation) both of: persistent hypotension requiring vasopressors to maintain MAP greater than or equal to 65 mm Hg, and lactate greater than or equal to 2 mmol/L.

You may not qualify if:

• pregnancy, congenital heart disease, artificial valve prosthesis, severe aortic or mitral pathology, atrial fibrillation, and inadequate image quality.

Sponsors & Collaborators

• Hospital Garcia de Orta: lead
• Instituto de Medicina Molecular João Lobo Antunes: collaborator

Study Sites (1)

Hospital Garcia de Orta

Lisbon, Almada, 2801-267, Portugal

Location

Related Publications (5)

• Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014 Apr 2;311(13):1308-16. doi: 10.1001/jama.2014.2637.

  PMID: 24638143 BACKGROUND

• Walley KR. Sepsis-induced myocardial dysfunction. Curr Opin Crit Care. 2018 Aug;24(4):292-299. doi: 10.1097/MCC.0000000000000507.

  PMID: 29846206 BACKGROUND

• Landesberg G, Gilon D, Meroz Y, Georgieva M, Levin PD, Goodman S, Avidan A, Beeri R, Weissman C, Jaffe AS, Sprung CL. Diastolic dysfunction and mortality in severe sepsis and septic shock. Eur Heart J. 2012 Apr;33(7):895-903. doi: 10.1093/eurheartj/ehr351. Epub 2011 Sep 11.

  PMID: 21911341 BACKGROUND

• Rapezzi C, Arbustini E, Caforio AL, Charron P, Gimeno-Blanes J, Helio T, Linhart A, Mogensen J, Pinto Y, Ristic A, Seggewiss H, Sinagra G, Tavazzi L, Elliott PM. Diagnostic work-up in cardiomyopathies: bridging the gap between clinical phenotypes and final diagnosis. A position statement from the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013 May;34(19):1448-58. doi: 10.1093/eurheartj/ehs397. Epub 2012 Dec 4.

  PMID: 23211230 BACKGROUND

• Gonzalez FA, Bacariza J, Varudo AR, Leote J, Mateus RM, Martins CM, Ribeiro MI, Sanfilippo F, Lopes LR, Almeida AG. Sepsis-induced myocardial dysfunction diagnosed with strain versus non-strain echocardiography parameters: incidence, evolution and association with prognosis. Ann Intensive Care. 2025 Sep 25;15(1):141. doi: 10.1186/s13613-025-01561-w.

  PMID: 40999250 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

For genetic analysis, blood will be withdrawn from patients at ICU admission and sent to a certified laboratory for whole-exome sequencing in collaboration with the Institute of Molecular Medicine (IMM).

MeSH Terms

Conditions

Shock, Septic; Cardiomyopathies

Interventions

Echocardiography; Genetic Testing

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Clinical Laboratory Techniques; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Filipe A Gonzalez, MD, PhD st.

  Hospital Garcia de Orta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior consultant of Internal Medicine and Intensive Medicine, PhD student

Study Record Dates

• First Submitted: September 15, 2022
• First Posted: September 23, 2022
• Study Start: September 20, 2022
• Primary Completion: February 26, 2024
• Study Completion: February 26, 2024
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)