Myocardial Injury and Severe Pneumococcal Pneumonia

Study Overview
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Brief Summary
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Hypothesis: The novo cardiovascular events (CVE)in patients with severe community-acquired pneumonia (CAP) are frequent (17%) and could be associated with both direct pneumococcal myocardial invasion, toxin delivery (pneumolysin) or different biomarkers (histones, NETs(neutrophil extracellular traps), IL (Interleukin)-1b,h-Fabp (heart-Fatty acid bindding protein) ).The CVE frequency and its impact on outcome in patients without prior heart disease (CP) has not been studied. Objectives:1) To determine the incidence of myocardian injury (MI) and CVE in patients with CAP without CP evaluated by non-invasive techniques (Echocardiograph and MRI) and biomarkers levels (Tn-I (Troponin I), h-Fabp, NT-proBNP (N-terminal pro-brain natriuretic peptide) histones, NETs, IL 1b); 2) To assess if DMA and CVE are related to the etiology and their impact on outcome , 3) To investigate the presence of myocardial scarring by MRI and its relationship with etiology and MI, and 4) To identify prognostic factors of DMA and CVE to determine level of risk.

Detailed Description
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Area: Intensive care unit (ICU) of the participating hospitals. Patients: Forty patients with CAP without heart disease history will be included consecutively (20 patients with pneumococcal CAP and 20 patients with non-pneumococcal CAP).Ten healthy volunteers (controls) are included. Variables: Epidemiological, clinical and hemodynamic variables are recorded. Presence of MI and CVE measured by echocardiography and by biomarkers will be evaluated during the ICU stay. Presence of scarring miocardic by MRI technique will be determined at month 6 since ICU admission. Statistical analysis: Categorical (Fisher's exact test) and continuous variables( Wilconxon and Anova) will be used to determine differences between them. The Pearson correlation, ROC (discriminatory power) and logistic regression analysis(independent association) will be used to determine the association between variables and outcome. A p-value of 0.05 will be considered significant.

Official Title
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Myocardial Injury in Severe Pneumococcal Pneumonia as a Cause of Mortality From Acute Cardiovascular Events

Conditions
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Pneumonia, Pneumococcal, Myocardial Ischemia

Intervention / Treatment
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* Diagnostic Test: Echocardiography
* Diagnostic Test: Cardiac Magnetic resonance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patients admitted to the ICU due to community-acquired pneumonia according to IDSA/ATS criteria - No history of heart diasese - Informed consent signed Exclusion Criteria: - Hospital or ventilator-associated pneumonia - Health care-associated pneumonia - Viral pneumonia - Bacterial/viral coinfection pneumonia - History of heart disease - Chronic administration of statins - Chronic administration of steorids (Prednisolone more 20 mg/day or equivalent) - No signed informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| pneumococcal pneumonia<br>Patients with community-acquired pneumonia due to S.pneumoniae. An Echocardiography will be performed to all patients (one per day during 7 days). A Cardiac magnetic resonance (MRI) will be performed during an acute episode and at month 6 since ICU admission. In addition a blood sample will be drawn daily (one per day during 7 days) to measure myocardial injury and inflammation systemic (interleukins) biomarkers. | Diagnostic Test: Echocardiography<br>* Standard protocols<br>* Other names: Heart resonance magnetic nuclear;Diagnostic Test: Cardiac Magnetic resonance<br>* MRI with late gadolinium increase and T1 mapping<br>* Other names: MRI;|
| non-pneumococcal pneumonia<br>Patients with community-acquired pneumonia due to S.pneumoniae. An Echocardiography will be performed to all patients (one per day during 7 days). A Cardiac magnetic resonance (MRI) will be performed during an acute episode and at month 6 since ICU admission. In addition a blood sample will be drawn daily (one per day during 7 days) to measure myocardial injury and inflammation systemic (interleukins) biomarkers. | Diagnostic Test: Echocardiography<br>* Standard protocols<br>* Other names: Heart resonance magnetic nuclear;Diagnostic Test: Cardiac Magnetic resonance<br>* MRI with late gadolinium increase and T1 mapping<br>* Other names: MRI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardian injury (scarring) in patients with CAP without cardiac disease (CP)history at 6 months of ICU admission | MRI with late gadolinium increase and t1 mapping techniques for to detect myocardial scarring | at 6 months | 
| Heart dysfunction in patients with CAP without cardiac disease (CP)history in the first week of ICU admission | Echocardiography with standard and strain techniques for to detect the presence of decrease in ejection fraction of both vetricules | at day 7 of ICU admission) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Temporal profile of the Troponin I as a cardiac injury biomarker in patients with CAP without cardiac disease (CP)history in the first week of ICU admission | Determination of serum troponin-I according to standard technique | once per day ( days 1 to 7 of ICU admission) | 
| Temporal profile of the N-terminal pro-brain natriuretic peptide(NT-proBNP) as a cardiac injury biomarker in patients with CAP without cardiac disease (CP)history in the first week of ICU admission | Determination of serum N-terminal pro-brain natriuretic peptide(NT-proBNP) according to standard technique | once per day (days 1 to 7 of ICU admission) | 
| Temporal profile of the heart- fatty acid binding protein (h-Fabp) as a cardiac injury biomarker in patients with CAP without cardiac disease (CP)history in the first week of ICU admission | Determination of serum heart- fatty acid binding protein (h-Fabp)according to standard technique | once per day (days 1 to 7 of ICU admission) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumococcal pneumonia, Acute cardiovascular events