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Severe Aortic Valve StenosisNCT06156592

Post Spinal Hemodynamic Changes in Aortic Stenosis and Mitral Regurgitation by VIS Index and Echocardiography

An observational study of Severe Aortic Valve Stenosis and Severe Mitral Valve Regurgitation, run by University of Manitoba at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will assess hemodynamic changes induced after spinal anesthesia by evaluating vasopressor inotropic requirements and variations in echocardiographic parameters in patients having severe aortic stenosis or severe mitral regurgitation undergoing aortic or mitral valve replacement surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cardiac valve replacement surgery under high spinal anesthesia combined with light general anesthesia
Type of treatment
Surgery or procedure
How many people
44 participants
Where
1 siteCanada
Study dates
1 Nov 2023to 26 Oct 2025
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Adult, Older adult

Study population: Adult patients admitted to St. Boniface Hospital, Winnipeg, Canada, a tertiary care hospital, for elective aortic or mitral valve repair over the period Oct 2023 to December 2025.

Who may be able to join

  • All patients over 18 years of age, irrespective of their gender or ASA physical status
  • With severe aortic stenosis or mitral regurgitation
  • Undergoing elective aortic or mitral valve repair or replacement
  • Eligible for spinal anesthesia up to T1-2 level block for their surgical procedure.
  • Able to provide written informed consent

Who cannot join

  • Contraindications to the administration of spinal anesthesia such as pre-existing coagulopathy, local sepsis at the site of insertion
  • Hypoxic (SaO2 < 95%) on room air
  • Unable to lie flat and with 15-degree trendelenburg
  • The apical four and five chamber window is not accessible on trans-thoracic echocardiography
  • Difficult airway requiring awake intubation
  • On dialysis
Show all 11Show fewer
  • Redo-valve surgery
  • Mixed valvular lesions (more than mild AR or MS)
  • Requiring more than one CABG or CPB duration more than 180 minutes
  • More than 3 segment Regional Wall Motion Abnormalities
  • Severe spine disorders

Trial locations and contacts

1 site in 1 country.

Canada1 site
  • Department of Anesthesiology, Perioperative and Pain Medicine, SBGH

    Winnipeg, Manitoba, R2H 2A6

Other trials in Canada

About this study

Official title: Prospective Observational Study to Compare Hemodynamic Alterations in Severe Aortic Stenosis and Severe Mitral Regurgitation After High Spinal Anesthesia in Patients Undergoing Aortic Valve and Mitral Valve Replacement Surgery

This study will assess hemodynamic changes induced after spinal anesthesia by evaluating vasopressor inotropic requirements and variations in echocardiographic parameters in patients having severe aortic stenosis or severe mitral regurgitation undergoing aortic or mitral valve replacement surgery.

Read the detailed description

Spinal anesthesia (SA) involves injecting local anesthetic into the intrathecal space. Since it was first described, understanding of the physiology and pharmacology of drugs acting within the subarachnoid space has improved. Physiological changes observed following SA are believed to be attributed to their blockade of peripheral and cardiac sympathetic fibers. The changes in cardiac output (CO) observed following SA were originally thought to be explained by the 'pre-load reduction' theory that describes a decrease in CO resulting from reduced venous return leading to arterial hypotension. However, this theory was questioned due to failed attempts to avoid SA induced hypotension by three preventative techniques: preloading with crystalloids or colloids, lower limb compression, and lateral tilt maneuvers (1). Additional studies and subsequent data led to further questioning of the pre-load reduction theory and supported a shift to an 'after-load reduction' theory. This proposes that hypotension following SA is a result of sympathetic blockade causing arterial dilatation (1,2). With this knowledge, it has traditionally been taught to avoid SA in severe aortic stenosis (AS) for risk of decreased coronary perfusion, while SA has been considered safe, or even beneficial in those with severe mitral regurgitation (MR). However, there is a paucity of real time evidence to help support these claims. Furthermore, individuals with experience in performing SA in patients with severe AS and/or MR have questioned the hemodynamic effects that are traditionally described (3).

With advancements in echocardiographic techniques, point of care ultrasound has emerged in critical care to become the standard for evaluating hemodynamic changes observed in hemodynamic instability or cardiovascular collapse (4). This provides an opportunity to assess CO, and its associated parameters including venous return, preload, afterload, and contractility, in real time. With this tool, one can compare the hemodynamic changes in patients with AS or MR before and after high SA given for their cardiac surgery for valve replacements or repair (AVR or MVR).

Hypothesis and Study Objectives:

This study may provide real time information to support or challenge traditional understanding of the hemodynamic changes seen following SA in those with severe AS or severe MR. Since, hemodynamic stability is goal in all patients after any type of anesthesia, the primary objective is to compare requirement of vasopressors, inotropes, and inodilators required to maintain desired hemodynamic goals (Mean arterial pressure 65-100 mmHg and HR 50-100/min) and to observe and compare hemodynamics alteration by using echocardiographic parameters of venous return, cardiac index (CI), preload, afterload, and cardiac contractility using myocardial performance index (Tei index) (5) before and after high SA in patients having predominant severe AS or MR. Furthermore, subgroup analysis will be conducted to compare hemodynamic parameters and medication requirements to meet target hemodynamic goals among patients with preserved and reduced left ventricular systolic function (for AS reduced LVEF < 50 %, for MR reduced LVEF < 60%).

Methodology:

This prospective observational study will be conducted at St. Boniface Hospital, Winnipeg, Canada. All adult patients above 18 years of age, irrespective of their gender, ASA physical status, and LVEF requiring SA up to T1-2 level block with light general anesthesia (GA) for their surgical procedures of AVR or MVR will be included. Exclusion criteria: Mixed valvular lesion (more than mild AR or MS), redo cardiac surgery, not eligible for fast tracking (i.e., anticipated post-surgical extubation time more than 10 hours (6) of successful uncomplicated surgery, unable of laying supine in 15-degree Trendelenburg, hypoxic patients (SaO2 less than 94% on room air), difficult airway requiring awake intubation, patients receiving dialysis, contraindication for transesophageal echo (TEE) or spinal anesthesia, significant deformity of thoracic and lumbar spine and poor TTE windows for data acquisition. Patients undergoing associated CABG for single vessel and without significant regional wall motion abnormalities on echo (no more than 3 segment involvement), will be included. Patients will be consented for the study once eligible participants are identified in the cardiac anesthesia PAC clinic.

All TTE parameters will be recorded in the apical 4 and 5 chamber views with a Phillips echo Apiq 7 machine. The following baseline echo parameters to be recorded will be linear dimensions of tricuspid valve (TV) and mitral valve (MV) annulus in 4C view left ventricular outflow tract (LVOT) in Plax view, and LVEF in apical 4C view and LV short axis view. The linear dimensions of TV and MV annulus and LVOT will also be confirmed on TEE views and final measurement will be relied on more crisp views. At baseline echo and repeat assessments, the parameters to be recorded will be velocity time integral (VTI) of LVOT, MV, TV, tricuspid annular plane systolic excursion (TAPSE) and mitral annular plane systolic excursion (MAPSE) on M-Mode, and tissue doppler imaging (TDI) of lateral TV and MV annulus. To calculate LV Tei index Doppler time intervals measured from MV inflow and LVOT Doppler tracings, as described by Tei and co-workers will be used (5). Tei index will also be calculated from TDI interrogation using 1.5 mm sample volume from lateral MV and TV for LV and RV (6,7). For LV Tei index mean of values from TDI and PWD will be used for analysis. No correction for HR variability will be applied for Tei index below HR 100/min (8). In patients with atrial fibrillation (AF), "pre ejection period (PEP)-derived MPI (Tei index)" will be calculated since the loss of mechanical atrial function does not allow measurement of isovolumic contraction time (IVCT) (9). On TEE, a mid-esophageal (ME) 4 and Deep TG views will be used post intubation for same Doppler and M mode parameters.

Among cardiac medications only beta blockers will be continued on am of surgery. Once in the operating room, all patients will have two intravenous lines, ECG, arterial line, central venous line, pulse oximetry, defibrillator pads, cerebral oximetry and patient state index (PSi) by Masio monitored. During the study period, Ringer's Lactate will be infused at a rate of 600ml/hr (100 ml infusion drive line and 500 ml/hr second iv line which will also be used for drug boluses). Intraoperative hemodynamic parameters will be automatically recorded by computer interphase system with Philips monitors. A high spinal will be given using 37.5 mg of 0.75% bupivacaine heavy with 20 mcg fentanyl and 250 mcg epimorphine in sitting position at the lumbar intervertebral spaces between the L2-3 or L3-4 vertebrae with 25 G Whitacre or Quincke needle. Patients will lie supine immediately afterwards, and sensory loss to ice will be performed every 15 seconds. Echo parameters with TTE will be recorded before spinal, at sensory loss between T10-12 in flat supine. Subsequently, the patient will be placed in 15-degree Trendelenburg (ensured by clinometer) and once sensory loss between T4-T8 occurs, a third TTE recording will be performed while patient being preoxygenated in preparation for GA. Afterwards, patients will be induced by general anesthesia (GA) in the Trendelenburg position, and a fourth echo recording will be performed by TEE under GA after putting CVL and first CVP reading is taken by keeping transducer at heart level in the mid axillary line. Final fifth TEE echo parameters will be recorded in final surgical position which will be flat supine with back up to 5 degrees.

A change in SBP or MAP equal to or less than 10% mmHg and HR equal to or less than 10% beats/min from readings before incision within one minute of skin incision and sternotomy will be considered "no response" and an effective sensory block unto T1.

General anesthesia will be induced by 0.02-0.03 mg/Kg midazolam (maximum 2 mg), 0.2-0.4 mg/Kg ketamine (maximum 20 mg), 0.3-0.5 mcg/Kg sufentanil, titrated dose of 1-3 mg/Kg propofol to loss of eye reflex, and rocuronium 1.0-1.2 mg/kg. Intubation will be preceded with 5 ml of 4% lignocaine spray on the vocal cords and in trachea. Post intubation anesthesia will be maintained by 50% oxygen with sevoflurane 1-2 % end tidal value titrated to PSI 30-50 on Massimo monitor, volume control ventilation targeting EtCO2 goal of 35-40 mmHg. During the study period target hemodynamics will be aimed at MAP between 65-100 mmHg and heart rate between 50-100 beats /min by use of various inotropic, inodilators and vasoactive cardiac drugs based on anesthesiologists' clinical judgement. Total dose of boluses and infusions of these drugs used during study period will be recorded for comparison as cumulated modified vasopressor inotropic inodilator score index during pre CPB, on CPB and post CPB period till patient leaves the operation room. This will be calculated as follows:

Total modified VIS score (pre CPB or on CPB or post CPB) = (total dopamine in mcg ) + (total dobutamine in mcg) + (10 x total milrinone in mcg) + (10,000 x total vasopressin unit) + (100 x total norepinephrine in mcg) + ( 100 x total epinephrine dose mcg) + (100 x total ephedrine dose in mg) + (10 x total phenylephrine dose in mcg) VIS index = Total modified VIS score / (weight in Kg x time in minutes)

Being tested
Cardiac valve replacement surgery under high spinal anesthesia combined with light general anesthesia
Keywords
mitral valve replacement, aortic valve replacement, spinal anesthesia, echocardiographic monitoring, aortic stenosis, mitral regurgitation
Medical subject headings
Aortic Valve Stenosis, Mitral Valve Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cardiac valve replacement surgery under high spinal anesthesia combined with light general anesthesiaProcedure or surgery

    Before induction of general anesthesia, a high spinal anesthesia will be given using 37.5 mg of 0.75% heavy bupivacaine with 20 mcg fentanyl and 250 mcg epimorphine in sitting position at the lumbar intervertebral spaces between the L2-3 or L3-4 vertebrae. Patients will lie supine immediately afterwards, and sensory loss to ice will be performed every 15 seconds. Subsequently, the patient will be placed in 15-degree Trendelenburg (ensured by clinometer). Following general anesthesia will be induced and trachea will be intubated after 5 ml of 4% lignocaine spray on vocal cords and trachea. Hemodynamics will be aimed at MAP between 65-100 mmHg and heart rate between 50-100 beats /min by use of various inotropic, inodilators and vasoactive cardiac drugs based on anesthesiologists' clinical judgement.

Study groups in NCT06156592
Study groupRoleWhat they receive
Severe aortic stenosis groupPatients with severe aortic stenosis who are undergoing open aortic valve replacement under high spinal in combination with light general anesthesia.
Receives: Procedure: Cardiac valve replacement surgery under high spinal anesthesia combined with light general anesthesia
Severe mitral regurgitation groupPatients with severe mitral regurgitation who are undergoing open mitral valve replacement under high spinal in combination with light general anesthesia.
Receives: Procedure: Cardiac valve replacement surgery under high spinal anesthesia combined with light general anesthesia

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To compare total inotropic, inodilators and vasopressor drug requirements by calculating the vasoactive-inotropic score (VIS) Index to maintain target stable hemodynamics in both groups

    Total modified VIS score (pre CPB or on CPB or post CPB) = (total dopamine in mcg ) + (total dobutamine in mcg) + (10 x total milrinone in mcg) + (10,000 x total vasopressin unit) + (100 x total norepinephrine in mcg) + ( 100 x total epinephrine dose mcg) + (100 x total ephedrine dose in mg) VIS index = Total modified VIS score / (weight in Kg x time in minutes)

    Measured: From spinal drug injection to the starting of cardiopulmonary bypass (CPB), during CPB surgery and post CPB up to the time when patient leaves operation room

  2. To compare changes in right and left ventricular myocardial performance index (Tei) in both groups

    Tei index for the left ventricle will be derived using Doppler interrogation MV and left ventricular outflow tract (LVOT) blood flows and for both RV and LV by tissue Doppler interrogation of TV and MV lateral annular plane motion on echocardiography in both groups

    Measured: Baseline pre-spinal, 2 minutes post spinal flat supine, 5 min post spinal trendelenburg 15 degree,10 minutes post general anesthesia at opening CVP pressure in trendelenburg 15 degree, 2 minute post surgical position flat supine with 5 degree back up

  3. To compare changes in Left Ventricular Outflow Tract (LVOT) Cardiac Index (CI) in both groups

    LVOT cardiac index will be derived pulse wave Doppler interrogation of LVOT flow, 2 dimensional LVOT area and heart rate by echocardiography

    Measured: Baseline pre-spinal, 2 minutes post spinal flat supine, 5 min post spinal trendelenburg 15 degree,10 minutes post general anesthesia at opening CVP pressure in trendelenburg 15 degree, 2 minute post surgical position flat supine with 5 degree back up

Secondary outcomes (6)
  1. Subgroup analysis of patients with preserved Left Ventricular Ejection Fraction (LVEF) and reduced LVEF for comparison of Tei index of right ventricle, and left ventricle, TAPSE, MAPSE and LVOT CI by echocardiography and VIS index to maintain target he

    Subgroup division will be done among all patients irrespective of primary valvular lesion based on LVEF which will be considered reduced if less than 50% in aortic stenosis and less than 60% in mitral regurgitation

    Measured: Similar pre-defined time points for echocardiography readings and VIS index durations as for primary end points.

  2. Assessment and determination of changes in other echocardiographic hemodynamic parameters of preload, after load after high spinal anesthesia in severe AS and severe MR and their comparison to baseline and between these two valvular pathologies.

    Echocardiographic measurements of TV flow, MV flow, and calculated preload and afterload from LV dimensions and CVP and arterial pressures will be derived using Laplace equation

    Measured: Baseline pre-spinal, 2 minutes post spinal flat supine, 5 min post spinal trendelenburg 15 degree,10 minutes post general anesthesia at opening CVP pressure in trendelenburg 15 degree, 2 minute post surgical position flat supine with 5 degree back up

  3. Assessment and determination of changes in other echocardiographic parameters of RV contractility after high spinal anesthesia in severe AS and severe MR and their comparison to baseline and between these two valvular pathologies.

    Echocardiographic measurements of TV annular plane systolic excursion (TAPSE) by M-mode application

    Measured: Baseline pre-spinal, 2 minutes post spinal flat supine, 5 min post spinal trendelenburg 15 degree,10 minutes post general anesthesia at opening CVP pressure in trendelenburg 15 degree, 2 minute post surgical position flat supine with 5 degree back up

  4. Assessment and determination of changes in other echocardiographic parameters of LV contractility after high spinal anesthesia in severe AS and severe MR and their comparison to baseline and between these two valvular pathologies.

    Echocardiographic measurements of MV annular plane systolic excursion (MAPSE) by M-mode application

    Measured: Baseline pre-spinal, 2 minutes post spinal flat supine, 5 min post spinal trendelenburg 15 degree,10 minutes post general anesthesia at opening CVP pressure in trendelenburg 15 degree, 2 minute post surgical position flat supine with 5 degree back up

  5. Comparison of pulse oximetry and cerebral oximetry changes during study period between AS and MR patients

    This will be done using pulse oximeter and cerebral oximeter by Masimo monitor

    Measured: Baseline, at echo reading time points, and every 15 minutes afterwards to the end of surgery in both the groups

  6. Comparison of any complications in both group and subgroups during study period

    Any arrhythmia, hemodynamic episode outside target, spinal anesthesia complications, any unforeseen complication

    Measured: From spinal drug injection to the starting of cardiopulmonary bypass (CPB), during CPB surgery and post CPB up to the time 48 hours in cardiac intensive care unit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Dec 2023
  2. Study start1 Nov 2023
  3. Primary completion26 Oct 2025
  4. Study completion26 Oct 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06156592
Sponsor's protocol ID
HS25925
Status last verified
Oct 2025
First submitted
24 Sep 2023
Last updated
6 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Johnson E. 'Advances in understanding and management in obstetric anaesthesia': The great myth of our times. Indian J Anaesth. 2017 Apr;61(4):285-288. doi: 10.4103/ija.IJA_209_17. No abstract available.

    PubMed 28515514
  • Langesaeter E, Rosseland LA, Stubhaug A. Continuous invasive blood pressure and cardiac output monitoring during cesarean delivery: a randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion. Anesthesiology. 2008 Nov;109(5):856-63. doi: 10.1097/ALN.0b013e31818a401f.

    PubMed 18946298
  • Bhat I, Arya VK, Mandal B, Jayant A, Dutta V, Rana SS. Postoperative hemodynamics after high spinal block with or without intrathecal morphine in cardiac surgical patients: a randomized-controlled trial. Can J Anaesth. 2021 Jun;68(6):825-834. doi: 10.1007/s12630-021-01937-z. Epub 2021 Feb 9.

    PubMed 33564993
  • Arya VK, Al-Moustadi W, Dutta V. Cardiac output monitoring - invasive and noninvasive. Curr Opin Crit Care. 2022 Jun 1;28(3):340-347. doi: 10.1097/MCC.0000000000000937. Epub 2022 Mar 11.

    PubMed 35275876
  • Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer RJ, Tajik AJ, Seward JB. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function--a study in normals and dilated cardiomyopathy. J Cardiol. 1995 Dec;26(6):357-66.

    PubMed 8558414
  • Cheng DC. Fast track cardiac surgery pathways: early extubation, process of care, and cost containment. Anesthesiology. 1998 Jun;88(6):1429-33. doi: 10.1097/00000542-199806000-00002. No abstract available.

    PubMed 9637632
  • Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015 Jan;28(1):1-39.e14. doi: 10.1016/j.echo.2014.10.003.

    PubMed 25559473
  • Poulsen SH, Nielsen JC, Andersen HR. The influence of heart rate on the Doppler-derived myocardial performance index. J Am Soc Echocardiogr. 2000 May;13(5):379-84. doi: 10.1016/s0894-7317(00)70007-1.

    PubMed 10804435
  • Su HM, Lin TH, Hsu PC, Chu CY, Lee WH, Lee CS, Lai WT, Sheu SH, Voon WC. Myocardial performance index derived from preejection period: a novel and feasible parameter in evaluation of cardiac performance in patients with permanent atrial fibrillation. Echocardiography. 2011 Nov;28(10):1081-7. doi: 10.1111/j.1540-8175.2011.01491.x. Epub 2011 Aug 19.

    PubMed 22077881

Questions about this trial

What is this clinical trial studying?

An observational study of Severe Aortic Valve Stenosis and Severe Mitral Valve Regurgitation, run by University of Manitoba at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To compare total inotropic, inodilators and vasopressor drug requirements by calculating the vasoactive-inotropic score (VIS) Index to maintain target stable hemodynamics in both groups (time frame: From spinal drug injection to the starting of cardiopulmonary bypass (CPB), during CPB surgery and post CPB up to the time when patient leaves operation room). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06156592, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2026.

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