SONOlysis in Risk REduction of Symptomatic and Silent Brain infarCtions dUring Cardiac surgEry
SONOlysis in Risk REduction of Symptomatic and Silent Brain infarCtions dUring Cardiac surgEry
The aim of the project is to demonstrate a fibrinolytic effect of sonothrombolysis (continual
 transcranial Doppler monitoring) using 2 MHz diagnostic probe on the reduction of risk of
 brain infarctions due to the activation of endogenous fibrinolytic system during cardiac
 surgery (CS). 120 patients indicated for CS (CABG or valve replacement) will be enrolled into
 the study in order to demonstrate a twenty-percent risk reduction of number and volume of
 brain infarctions detected using MRI examination 24 hours after CEA or CS in 5% level of
 significance. Patients will be randomized - subgroup 1 will undergo a 40-240minute
 non-diagnostic TCD monitoring during CS, subgroup 2 will undergo interventions without TCD
 monitoring.

 The aim of the project is a concordance with the aim No 1 of the Resort Program of a Research
 and Development: "Improvement of quality of life of patients using the modern therapeutic
 methods but with relative small positive effect of quality of life". The aim of the project
 is in concordance with a priority of announced public grant competition: "Development of the
 new therapeutic methods of cardiovascular disorders, especially coronary heart disease and
 stroke". Confirmation of our hypothesis that sonothrombolysis is able to activate endogenous
 fibrinolytic system during CS with consecutive reduction of the number and volume of brain
 infarcts, can lead to the increase of the safety of CS in patients. We can presume that up to
 50% of patients indicated for CS can be treated using these methods in the future.
AIM OF THE PROJECT The aim of the project is to demonstrate an effect of continual TCD
 monitoring using 2 MHz diagnostic probe with maximal diagnostic energy on the reduction of
 risk of brain microinfarctions due to the activation of endogenous fibrinolytic system and
 mechanical effect on emboli during CS.

 The aim of the project is a concordance with the aim No 1 of the Resort program of a research
 and development in the years 2010-2015: "Improvement of quality of life of patients using the
 modern therapeutic methods but with relative small positive effect of quality of life". The
 aim of the project is in concordance with a priority of announced public grant competition:
 "Development of the new therapeutic methods of cardiovascular disorders, especially coronary
 heart disease and stroke".

 HYPOTHESIS Sonothrombolysis lead to activation of fibrinolytic system in both healthy
 volunteers and acute stroke patients. In acute stroke patients, mechanical effect of
 sonothrombolysis is the second effect leading to acceleration of occluded artery
 recanalization. We hypothesize that combination of mechanical effect and activation of
 fibrinolytic system durin sonothrombolysis (TCD monitoring) during CS will lead to
 recanalization of small arterial occlusions caused by microembolization during intervention.
 The result will be reduction of volume and the number of brain infarctions in the territory
 of the monitored MCA.

 120 patients indicated for CS will be enrolled into the study in order to demonstrate a
 twenty-percent risk reduction of number and volume of brain infarctions in the territory of
 athe monitored MCA detected using MRI examination 24 hours after CS in 5% level of
 statistical significance. Patients will be randomized into 2 subgroups. Subgroup 1 will
 undergo non-diagnostic TCD monitoring during CS. Subgroup 2 will undergo CS without TCD
 monitoring.

 PATIENTS AND METHODS Patients: 120 patients indicated for CS (isolated coronary artery bypass
 surgery or isolated heart valve surgery) will be enrolled into the study during a 3-year
 period. All 120 patients will be randomized for standard CS and TCD monitored CS.

 Clinical examinations: Physical and neurological examinations including evaluating of
 neurological impairment of neurological deficit in NIHSS scale, modified Rankin scale and
 cognitive testing (Mini Mental State Examination, Clock drawing test) will be performed
 before and 24 - 72 hours after CS.

 Randomization: Randomization using computer generated random allocation will be used,
 separately for coronary artery bypass surgery and valve surgery patients.

 Sonothrombolysis: In patients randomized into sonothrombolysis subgroup, MCA segment in depth
 55 mm will be monitored for 40 - 240 minutes using a diagnostic 2 MHz probe with maximal
 diagnostic energy. Non-diagnostic TCD monitoring will be performed without detection of
 microembolic signals or detection of changes in blood flow. The second (control) subgroup
 will undergo a standard CS without sonothrombolysis.

 MRI protocol will consists of 4 sequences: 1. Localizer; 2. T2TSE; 3. FLAIR; 4. DWI.
 Sequences 1-3 will be applied in the same level, they will have the same slice thickness and
 the same cut number. The slice thickness comprises its own cut thickness (5 mm) + distant
 factor (30%). Standard number of slices is 19. Standard slice level is considered to be a
 modified level of skull base due to the minimalization of distant artifacts EPI sequence.
 T2TSE: TR=4000/TE=99/ETL=9, FOV 230, FOV ph. 75%, matrix 256x256. FLAIR: 8050/112/ETL=21/2
 conc., FOV 230, FOV ph. 76,6%, matrix 256x151. EPI-DWI: 4200/139/EPI f.=96/6 av., FOV 230,
 FOV ph. 100%, phase enc. direction A-P, matrix 128x96 with interpolation, phase partial
 Fourier 6/8, Bw 1346 Hz/Px, echo spacing 0.83 ms, TA. Sequence called "trace" with three
 types of MR pictures in every slice: (a) T2*EPI b=0; (b) DWI b=500; (c) DWI b=1000. The
 fourth type of images automatically created an ADC map (in-line postprocessing). DWI show a
 middle (average) diffusivity of every point of examined brain tissue when b value is 500 and
 1000. This sequence is applied in order to assess hemorrhage (T2*EPI) and monitor sites of
 reduced diffusion (DWI, b=500 and 1000). New infarctions will be evaluated only in the
 territory of treated ICA.

 Adverse effects: All adverse effects during 1 month after UM will be registered, especially
 all causes for new admissions to the hospital, worsening of neurological symptoms (>4 points
 in NIH stroke scale), brain edema, symptomatic and asymptomatic intracranial bleeding
 detected in control brain MRI.

 Study protocol has been approved by the Ethics Committees in accordance with the principles
 and guidelines of the Declaration of Helsinki, 1975.
Inclusion Criteria:

 -  age 40-90 years,

 -  sufficient temporal bone window for TCD with detectable blood flow in MCA,

 -  independent patient (modified Rankin score 0-2),

 -  informed consent signed by the patient,

 -  CS will be performed as an elective surgery with an extracorporeal circulation

 Exclusion Criteria:

 -  contra-indication for MRI examination (pace-maker, implanted metal material,
 claustrophobia),

 -  emergent surgery,

 -  acute myocardial infarction,

 -  combined cardiac surgery,

 -  combined cardiac and carotid surgery