Ignite Creation Date:
2024-05-06 @ 3:28 PM
Last Modification Date:
2024-10-26 @ 1:50 PM
Study NCT ID:
NCT04641611
Status:
COMPLETED
Last Update Posted:
2024-04-09
First Post:
2020-11-11
Brief Title:
Effect of Venous Cannulation on the Incidence of Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass
Sponsor:
Dr Jean-Francois Morin
Organization:
Jewish General Hospital
Study Overview
Official Title:
Effect of Venous Cannulation Technique on the Incidence of Post-operative Atrial Fibrillation in Patients Undergoing Elective Coronary Artery Bypass Grafting A Pilot Randomized Controlled Trial
Status:
COMPLETED
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Context Atrial fibrillation is the most frequent arrhythmia following coronary artery bypass grafting POAF is associated with worse outcomes following CABG In addition recurrence of AF is associated with longer hospital stay and higher rate of neurological and renal complications compared to a single episode of AF Objective To estimate the proportion of eligible people who are willing to participate number of participants who drop out of the trial and use the results of this study to inform a larger study
Study Design
Pilot randomized controlled trial Patients will be blinded to the intervention
Participants
The study population will include 40 patients Patients admitted to the Jewish General Hospital for elective coronary artery bypass grafting from May 2021 will be included in the study Patients will be included if they were in sinus rhythm with a HR 50 bpm undergoing on-pump coronary artery bypass grafting and hemodynamically stable Patients will be excluded from the study if they meet any of the following criteria Second or third degree heart block LVEF 35 left atrial volume index 42 mlm2 right atrial volume index 47 mlm2 any degree of tricuspid regurgitation any degree of right ventricular dysfunction emergency or minimally invasive operation concurrent valve operation history of atrial fibrillation or previous cardiac surgery
Study Interventions and Measures Patients will be randomly assigned to one of two treatment groups according to the venous cannulation technique used during surgery Group A will undergo cavoatrial cannulation with a 2-stage venous cannula Group B will undergo bicaval cannulation with snares Similar surgical methods will be used in all treatment groups
The primary endpoint will be defined as any episode of atrial fibrillation in any participant lasting 5 minutes in duration or any episode leading to hemodynamic compromise SBP90 mmHg or causing symptoms angina or dyspnea Atrial fibrillation will be diagnosed using telemetry and a 12-lead ECG Patients will be followed up in 1 month with a 12-lead ECG to determine their rhythm The secondary endpoints are the development of RV dysfunction tricuspid regurgitation and any increase in left atrial volume index as detected by post-operative transthoracic echocardiography
Study Design
Pilot randomized controlled trial Patients will be blinded to the intervention
Participants
The study population will include 40 patients Patients admitted to the Jewish General Hospital for elective coronary artery bypass grafting from May 2021 will be included in the study Patients will be included if they were in sinus rhythm with a HR 50 bpm undergoing on-pump coronary artery bypass grafting and hemodynamically stable Patients will be excluded from the study if they meet any of the following criteria Second or third degree heart block LVEF 35 left atrial volume index 42 mlm2 right atrial volume index 47 mlm2 any degree of tricuspid regurgitation any degree of right ventricular dysfunction emergency or minimally invasive operation concurrent valve operation history of atrial fibrillation or previous cardiac surgery
Study Interventions and Measures Patients will be randomly assigned to one of two treatment groups according to the venous cannulation technique used during surgery Group A will undergo cavoatrial cannulation with a 2-stage venous cannula Group B will undergo bicaval cannulation with snares Similar surgical methods will be used in all treatment groups
The primary endpoint will be defined as any episode of atrial fibrillation in any participant lasting 5 minutes in duration or any episode leading to hemodynamic compromise SBP90 mmHg or causing symptoms angina or dyspnea Atrial fibrillation will be diagnosed using telemetry and a 12-lead ECG Patients will be followed up in 1 month with a 12-lead ECG to determine their rhythm The secondary endpoints are the development of RV dysfunction tricuspid regurgitation and any increase in left atrial volume index as detected by post-operative transthoracic echocardiography
Detailed Description:
Introduction
Atrial fibrillation is the most frequent arrhythmia following coronary artery bypass grafting Its incidence following cardiac surgery is estimated to be between 10-601-5 The incidence is lower in patients undergoing isolated coronary artery bypass grafting 25-30 compared to valve operations 267 It most commonly occurs in the first four days following cardiac surgery158 Despite many efforts to predict and prevent postoperative AF the incidence has not changed over the past decades1-59
Although in the past it was thought of as a benign self-limiting complication9 atrial fibrillation after cardiac surgery has been shown to be associated with worse outcomes compared to patients who remain in sinus rhythm postoperatively It leads to increased length of hospital and ICU stay higher rate of stroke wound infection renal failure myocardial infarction and has a significant effect on early and long-term mortality2-4 In addition recurrence of AF is associated with longer hospital stay and higher rate of neurological and renal complications compared to a single episode of AF 5
12Mechanisms of POAF
Several studies have investigated the underlying mechanisms involved in development of post-operative atrial fibrillation However these mechanisms remain largely unclear It is believed that atrial fibrillation is caused by reentry of multiple wavelets of excitation in the presence altered atrial refractoriness This makes ectopic beats originating from foci in the pulmonary veins more likely to trigger an episode of atrial fibrillation 10-12
In their comprehensive review Maesen B et al illustrate the various factors that lead to the development of atrial fibrillation It is triggered by an interaction of acute factors of surgery and pre-existing factors chronic in the patient 1 In other words factors related to cardiac surgery such as inflammation oxidative stress and sympathetic activation together with the presence of an atrial substrate predispose to the development of POAF 112 The most common co-morbid conditions the increase the susceptibility of AF are hypertension heart failure mitral valve disease and coronary artery disease12 These co-morbidities also lead to atrial dilation which is a key factor in the development of an atrial substrate12
To support this hypothesis Maesen B et al explain that drugs which increase sympathetic activity in the heart such as milrinone dobutamine and dopamine increase the incidence of POAF They also demonstrate that perioperative beta-blockers reduced POAF incidence This is supported a meta-analysis of 33 randomized controlled trials investigating beta-blocker treatment for prevention of POAF Perioperative beta-blockers led to a reduction in the incidence of postoperative AF13
Maesen B et al also argue that inflammation and oxidative stress -caused by surgical trauma and use of cardiopulmonary bypass- contribute to the development of POAF by demonstrating that treatment with ascorbic acid or N-acetyl cysteine both antioxidants reduced the incidence of POAF1
In addition drugs with anti-inflammatory properties such as corticosteroids and statins have -in many studies- reduced the incidence of POAF1 This is also supported by various studies that found an association between AF and high levels of inflammatory markers such as C-reactive protein and Interleukin-614
13Risk factors for POAF
Several studies have investigated the risk factors that could lead to the development of postoperative AF and attempted to provide a risk stratification model515-17 These attempts were unsuccessful in establishing a comprehensive predictive model for POAF
The most consistent preoperative risk factor for POAF in those studies is older age 515-17 Age has been shown to be most strongly associated with development of POAF The studies frequently mention the following as pre-operative factors prior history of AF congestive heart failure COPD diabetes mellitus left ventricular hypertrophy and left atrial enlargement
In their prospective study of patients undergoing cardiac surgery Chu et al found that a CHADS-VASc score of more than 2 Congestive heart failure Hypertension blood pressure 14090 mmHg or treated hypertension on medication Age 75years diabetes mellitus prior Stroke or transient ischemic attack or thromboembolism vascular disease Age 65 to 74 years Sex category female gender was associated with increased incidence of POAF 17
Perrier et al confirmed these findings in their cohort study of 1481 patients who underwent isolated CABG8 Additionally they have found that obesity renal failure preoperative beta-blockers and preoperative antiplatelet therapy to be independent risk factors for POAF 8 This is in contrast to most studies which found that preoperative beta-blockers decreased the incidence of POAF
In a study by Avi et al pre-operative right ventricular dysfunction as measured by RV myocardial performance index MPI -which is a measurement of RV systolic and diastolic function- was demonstrated to be a predictor of POAF in patients undergoing isolated CABG6
With regards to postoperative factors a multicenter observational study found that postoperative withdrawal of beta-blockers or ACE inhibitors correlate with increased incidence of POAF 5
The role of potassium and magnesium supplementation to treat hypokalemia and hypomagnesaemia in order to prevent ventricular arrhythmias after myocardial infarction is well recognized In addition low serum magnesium has been shown to be associated with increased incidence of atrial fibrillation in the general population18 However low serum magnesium hasnt been well established as a predictor of POAF 1920 The findings of studies on the beneficial effects of prophylactic administration of magnesium to prevent atrial fibrillation post cardiac surgery have been conflicting1321-23 A meta-analysis of 35 RCTs by Fairly et al found that magnesium supplementation reduced the risk of atrial fibrillation postoperatively21 However their analysis was limited by significant heterogeneity between the studies While another meta-analysis failed to show a prophylactic effect of magnesium or potassium supplementation against PAOF22 Cook et al performed a meta-analysis of 5 RCTs after excluding the trials with methodological problems they failed to show a prophylactic effect of magnesium against AF23
Furthermore Kalus et al and Matsuura et al investigated the impact of volume overload on the incidence of AF they found that increased fluid balance on the first or second postoperative days after cardiac surgery was an independent predictor of POAF 2425 Both studies hypothesized that volume overload will lead to left atrial dilation and thus predispose to AF However neither of the studies had recorded measurements of left atrial size
Few studies have investigated the intraoperative factors of POAF It is known that concurrent valve surgery increases the risk of POAF517 Other risk factors found consistently in the literature include cardiopulmonary bypass and aortic cross clamp times10151626 A multicenter study found that bicaval cannulation and pulmonary vein venting might be associated with increased risk of POAF 5 In addition an earlier retrospective study found that snared bicaval cannulation was associated with increased incidence of postoperative atrial arrhythmias in patients receiving high volume crystalloid cardioplegia However this effect was not observed when low volume cardioplegia was used to compare unsnared bicaval cannulation with cavoatrial cannulation9
It has been postulated that atrial incision and atrial ischemia during surgery lead to alterations of atrial conduction and refractoriness thereby predisposing to the development of POAF 10 In addition Tchervenkov et al found an association between persistence of residual atrial electrical activity during cardioplegic arrest and post-operative atrial tachyarrhythmia27 It might be that atrial activity during cardioplegic arrest -which could be due to inadequate atrial protection - resulted in atrial ischemia which in turn contributes to POAF development 27 It has been demonstrated that return of relatively warm venous blood to the right atrium and ventricle may lead to myocardial warming thereby diminishing the protective effect of cardioplegia Older animal studies have shown conflicting results regarding the optimal cannulation technique to reduce myocardial rewarming during arrest2829 Furthermore no study prospectively investigated the effect of different cannulation techniques on post-operative atrial tachyarrhythmia
Due to the scarcity of data regarding the intraoperative risk factors of POAF these factors are not well recognized and preventative strategies are therefore not well established
2 Objectives To estimate the proportion of eligible people who are willing to participate the number of participants who drop out of the trial and use the results of this study to inform a larger study
3 Study design 31 Recruitment and sample size Participants will be screened to enter the study in clinic by the principal investigator who is cardiac surgeon Only the principal investigators patients who meet inclusion criteria will be considered in the study Eligibility to enter the study will be determined during the patients consultation in clinic
Considering we usually operate on 1 or 2 patients per week who meet inclusion criteria We believe that 20 patients per group is reasonable to assess feasibility of recruitment and protocol implementation
32 Study population and study procedure
Patients admitted to the Jewish General Hospital for elective coronary artery bypass grafting from January 2021 will be included in the study Patients will be screened in clinic prior to admission The study population will include 40 patients that will be randomly assigned to one of two treatment groups according to the venous cannulation technique used during surgery Group A will undergo cavoatrial cannulation with a 2-stage venous cannula Group B will undergo bicaval cannulation with snares
33 Intervention Bicaval cannulation will be performed through in the right atrium Small tapes are passed around the SVC and IVC Two purse string sutures are placed in the superior and inferior portions of right atrium Two small incisions are made inside the purse string sutures The SVC and IVC are cannulated through the superior and inferior incisions respectively The purse string sutures and small tapes passed through small tubes and snared The small tapes snare will act as a tourniquet to prevent venous return to the right atrium Bicaval cannulation is performed in cases of mitral and tricuspid valve operations to provide a bloodless operative field superior drainage of venous blood and potentially better protection of the heart compared to cavoatrial cannulation Similar surgical methods will be used in all treatment groups We will use a standard sternotomy incision to access the heart the distal ascending aorta be will cannulated Antegrade Del Nido cardioplegia will be used to arrest the heart under normothermia The left internal mammary artery will be grafted to the left anterior descending artery For the other grafts the left radial artery and saphenous venous grafts will be used where appropriate The saphenous vein will be harvested endoscopically and the radial artery will be harvested using an open technique Pre-operative beta-blockers will be continued to the day of surgery and re-started on the first post-operative day if heart rate and blood pressure were permissible
34 Randomization and blinding Patients will be screened in clinic They will be blinded to their treatment and will be prospectively randomized on hospital admission by simple randomization using a random numbers table Randomization will be performed by the principal investigator
35 Study measurements Patients data including demographics number of diseased coronary arteries and comorbidities such as presence of hypertension chronic kidney disease diabetes mellitus peripheral vascular disease previous stroke or myocardial infarction will be collected Operative data including patients temperature cardiopulmonary bypass time cross-clamp time aortic and venous cannulation technique number and location of bypasses will also be collected Echocardiographic parameters will be collected preoperatively intra-operatively and post-operatively These will include left ventricular ejection fraction right ventricular function left and right atrial volume indices RV myocardial performance index MPI and the presence of valvular heart disease Postoperative data will include serum electrolytes cardiac biomarkers volume status and beta-blocker use Postoperative echocardiogram will be done between POD 3-5 and while the heart is in sinus rhythm and with a heart rate 100bpm whenever possible
38 Data reporting Baseline and demographic data will be summarized by standard descriptive summaries eg means and standard deviations for continuous variables and percentages for categorical variables Hypothesis testing will not be performed as this is a feasibility study and the sample size to too small to yield significant conclusions
4 Confidentiality Informed consent will be taken in clinic by the principal investigator during participants visit Participants will be informed that theyre able to withdraw from the study at anytime pre-operatively An additional consent form separate from the regular operation consent form will be used for the study
Data will be collected in a paper data collection form which will then be transferred to a secure excel document The excel document will be password protected Paper forms will be placed in a secure cabinet in a locked office Only members of the research team will have access to the electronic and paper forms
5 Risk Assessment The risks associated with bicaval cannulation are minimal There is potential for increased risk of bleeding because of the need for two incisions instead of one Since were cannulating the SVC and IVC indirectly through atrial incisions these potential bleeding sites can be easily seen and controlled intra-operatively
There is a possibility of increased incidence of atrial fibrillation post-operatively in the intervention group Although uncommon some surgeons routinely perform bicaval cannulation for CABG
Participants may benefit from the intervention if it leads to decreased rate of POAF Thus avoiding the potential sequelae of AF and the side effects of treatment
6 PUBLICATION We plan to use the data obtained in this study for publication in a peer-review journal We may present the findings of the study in scientific conferences No identifiable information will be published
Appendix A Consent form
Study Title Effect of venous cannulation technique on the incidence of post-operative atrial fibrillation in patients undergoing elective coronary artery bypass grafting A pilot randomized controlled trial
Principle investigators Jean-Francois Morin MD Husain Esmaeil MD Alex Alojko Study Site Jewish General Hospital Address 3755 Chemin de la Côte-Sainte-Catherine Montréal QC H3T 1E2 Telephone 514 340-8222
Introduction You are being asked to participate in a research study Before agreeing to participate it is important that you read the following explanation of this study
The decision to participate in this study is up to you Your participation is completely voluntary Your decision will not affect your relationship with your regular doctor or your current or future medical care
Please read this form carefully Feel free to discuss the study with your family friends and healthcare provider before you make your decision whether to participate Ask about anything you dont understand or would like explained better Take time to decide whether or not you want to take part in this study and ask the study doctor or study staff as many questions about the study as you would like
Background and purpose You are being asked to take part in this study because you have been diagnosed with coronary artery disease and will undergo coronary artery bypass grafting
Atrial fibrillation is a type of heart arrhythmia that occurs in about 30 of patients undergoing coronary artery bypass grafting This rhythm problem could cause a clot to form in the heart this clot can travel to brain and cause a stroke Atrial fibrillation is a treatable condition The treatment method depends on the clinical situation It is usually treated with medications that either controls the speed or the rhythm of the heart If the arrhythmia causes severe symptoms such as chest pain dizziness or hypotension low blood pressure it is sometimes treated with an electrical current called electrical cardioversion to restore the heart to its normal rhythm
During heart surgery the heart will be stopped in order to perform the coronary artery bypass surgery The heart will be connected to a heart-lung machine also called cardiopulmonary bypass machine This machine takes over the job of the heart and lungs A plastic tube will be connected to right upper chamber of the heart called the right atrium to the machine this tube is called the venous cannula the tube carries blood from the heart into an oxygenator where it will be oxygenated The oxygenated blood is pumped into the body through a tube connected to the aorta the bodys main blood vessel
Another method of the venous cannulation is by connecting two tubes to the superior vena cava and inferior vena cava the two major veins carrying blood returning from the body to the right atrium of the heart This is the same method used for mitral and tricuspid valve operations
The purpose of this study is to look into the effect of different venous cannulation methods on the occurrence of atrial fibrillation a type of arrhythmia post coronary artery bypass grafting This study has 2 groups You will be randomly assigned to one of the two groups The first group will have the venous cannula connected to the right atrium which is the standard method The second group will have the venous cannula connected to the superior and inferior vena cava and a tie is secured around the cannula so that no blood passes into the right atrium instead the blood goes to the heart-lung machine
Potential Risks
There are potential risks to you by taking part in this study The rate of occurrence of atrial fibrillation heart arrhythmia could be higher in the treatment group you are assigned to The bleeding risk is theoretically higher since we are making an incision in 2 areas to insert the cannulas instead of a single incision in the standard method If bleeding occurs you might need a blood transfusion or in uncommonly you might need to be re-operated on to control the bleeding In addition there are some risks inherent to the coronary artery bypass grafting surgery which include bleeding heart attack heart rhythm problems heart failure which is inadequate pumping of blood by the heart Depending on the cause of the heart attack It can be managed with medications going back to surgery or by coronary angioplasty and placing a stent Heart failure is treated with medications
Other potential risks of coronary artery bypass grafting include liver problems elevated liver enzymes due to inadequate blood supply during the operation kidney injury due to inadequate blood supply during the operation Liver and kidney complications are usually managed with monitoring of their functions
Other risks inherent to the surgery include lung problems such as lung infection fluid collecting in the lungs or inability to disconnect the ventilator machine after the operation due to inability of the lungs to oxygenate the blood on their own and other uncommon risks such as stroke and death
Potential Benefits
You may benefit as a result of your participation in this study The rate of atrial fibrillation could be lower in the treatment group you are assigned to However there is no assurance that you will benefit from your participation in this study Results from this study may benefit other patients in the future
Alternative Treatments
This clinical study is for research purposes only You do not have to participate in the study to receive treatment for coronary artery disease The other option is a standard venous cannulation method in which the right atrium is cannulated
Voluntary ParticipationWithdrawal Your decision to participate in this clinical research study is voluntary You may choose not to participate or you may withdraw from the study for any reason at any time without penalty You should tell the study doctor or study team if you decide to leave the study
The study doctor can stop the study or your participation in the study at any time without your consent if it appears to be medically harmful to you if the study is cancelled or for administrative reasons
Confidentiality As part of this research we will collect personal information from you this means information that can identify you In order to protect your privacy all information collected will remain confidential to the extent permitted by law Your identifiable health information is protected by a law If the results of this study are published or presented at meetings you will not be identified
For monitoring control protection and security purposes your research study file could be checked by persons authorized by the Research Ethics Committee of the CIUSSS du Centre-Ouest-de-lÎle de Montréal These persons are bound by a confidentiality agreement
For all questions concerning your rights during your participation in this study or if you have any complaints or comments regarding your experience in taking part in this research study you can contact the Local Commissioner of Complaints and Quality of Service of the CIUSSS Centre-Ouest-de-lÎle-de-Montréal or the ombudsman of the institution at 514 340-8222 ex 24222
STATEMENT OF CONSENT
Study title Effect of venous cannulation technique on the incidence of post-operative atrial fibrillation in patients undergoing elective coronary artery bypass grafting A pilot randomized controlled trial
PARTICIPANT STATEMENT
I understand the information that was explained to me as contained in this consent form All my questions were answered to my satisfaction I will receive a copy of this signed consent form My participation is voluntary and I can withdraw from the research study at any time without any consequences and without having to give a reason Withdrawing from this research study at any time will not affect my medical care now or later in any way By signing this consent form I do not give up any of my legal rights
I agree to participate in this research study
Name of Participant
Signature Date
RESEARCHER STATEMENT
I as the person obtaining consent certify that I have explained to the participant or hisher legal representative where applicable the research study information contained in this consent form and have answered all questions I have clearly explained to the participant that she is free to withdraw at any time without providing a reason and without any consequences I commit together with the members of the research team to respect all conditions described in this consent form and to give a signed copy of the consent form to the participant
Name and signature of the researcher or person delegated to obtained consent
Date
TranslatorWitness if applicable
Name and signature of translatorwitness Date
Atrial fibrillation is the most frequent arrhythmia following coronary artery bypass grafting Its incidence following cardiac surgery is estimated to be between 10-601-5 The incidence is lower in patients undergoing isolated coronary artery bypass grafting 25-30 compared to valve operations 267 It most commonly occurs in the first four days following cardiac surgery158 Despite many efforts to predict and prevent postoperative AF the incidence has not changed over the past decades1-59
Although in the past it was thought of as a benign self-limiting complication9 atrial fibrillation after cardiac surgery has been shown to be associated with worse outcomes compared to patients who remain in sinus rhythm postoperatively It leads to increased length of hospital and ICU stay higher rate of stroke wound infection renal failure myocardial infarction and has a significant effect on early and long-term mortality2-4 In addition recurrence of AF is associated with longer hospital stay and higher rate of neurological and renal complications compared to a single episode of AF 5
12Mechanisms of POAF
Several studies have investigated the underlying mechanisms involved in development of post-operative atrial fibrillation However these mechanisms remain largely unclear It is believed that atrial fibrillation is caused by reentry of multiple wavelets of excitation in the presence altered atrial refractoriness This makes ectopic beats originating from foci in the pulmonary veins more likely to trigger an episode of atrial fibrillation 10-12
In their comprehensive review Maesen B et al illustrate the various factors that lead to the development of atrial fibrillation It is triggered by an interaction of acute factors of surgery and pre-existing factors chronic in the patient 1 In other words factors related to cardiac surgery such as inflammation oxidative stress and sympathetic activation together with the presence of an atrial substrate predispose to the development of POAF 112 The most common co-morbid conditions the increase the susceptibility of AF are hypertension heart failure mitral valve disease and coronary artery disease12 These co-morbidities also lead to atrial dilation which is a key factor in the development of an atrial substrate12
To support this hypothesis Maesen B et al explain that drugs which increase sympathetic activity in the heart such as milrinone dobutamine and dopamine increase the incidence of POAF They also demonstrate that perioperative beta-blockers reduced POAF incidence This is supported a meta-analysis of 33 randomized controlled trials investigating beta-blocker treatment for prevention of POAF Perioperative beta-blockers led to a reduction in the incidence of postoperative AF13
Maesen B et al also argue that inflammation and oxidative stress -caused by surgical trauma and use of cardiopulmonary bypass- contribute to the development of POAF by demonstrating that treatment with ascorbic acid or N-acetyl cysteine both antioxidants reduced the incidence of POAF1
In addition drugs with anti-inflammatory properties such as corticosteroids and statins have -in many studies- reduced the incidence of POAF1 This is also supported by various studies that found an association between AF and high levels of inflammatory markers such as C-reactive protein and Interleukin-614
13Risk factors for POAF
Several studies have investigated the risk factors that could lead to the development of postoperative AF and attempted to provide a risk stratification model515-17 These attempts were unsuccessful in establishing a comprehensive predictive model for POAF
The most consistent preoperative risk factor for POAF in those studies is older age 515-17 Age has been shown to be most strongly associated with development of POAF The studies frequently mention the following as pre-operative factors prior history of AF congestive heart failure COPD diabetes mellitus left ventricular hypertrophy and left atrial enlargement
In their prospective study of patients undergoing cardiac surgery Chu et al found that a CHADS-VASc score of more than 2 Congestive heart failure Hypertension blood pressure 14090 mmHg or treated hypertension on medication Age 75years diabetes mellitus prior Stroke or transient ischemic attack or thromboembolism vascular disease Age 65 to 74 years Sex category female gender was associated with increased incidence of POAF 17
Perrier et al confirmed these findings in their cohort study of 1481 patients who underwent isolated CABG8 Additionally they have found that obesity renal failure preoperative beta-blockers and preoperative antiplatelet therapy to be independent risk factors for POAF 8 This is in contrast to most studies which found that preoperative beta-blockers decreased the incidence of POAF
In a study by Avi et al pre-operative right ventricular dysfunction as measured by RV myocardial performance index MPI -which is a measurement of RV systolic and diastolic function- was demonstrated to be a predictor of POAF in patients undergoing isolated CABG6
With regards to postoperative factors a multicenter observational study found that postoperative withdrawal of beta-blockers or ACE inhibitors correlate with increased incidence of POAF 5
The role of potassium and magnesium supplementation to treat hypokalemia and hypomagnesaemia in order to prevent ventricular arrhythmias after myocardial infarction is well recognized In addition low serum magnesium has been shown to be associated with increased incidence of atrial fibrillation in the general population18 However low serum magnesium hasnt been well established as a predictor of POAF 1920 The findings of studies on the beneficial effects of prophylactic administration of magnesium to prevent atrial fibrillation post cardiac surgery have been conflicting1321-23 A meta-analysis of 35 RCTs by Fairly et al found that magnesium supplementation reduced the risk of atrial fibrillation postoperatively21 However their analysis was limited by significant heterogeneity between the studies While another meta-analysis failed to show a prophylactic effect of magnesium or potassium supplementation against PAOF22 Cook et al performed a meta-analysis of 5 RCTs after excluding the trials with methodological problems they failed to show a prophylactic effect of magnesium against AF23
Furthermore Kalus et al and Matsuura et al investigated the impact of volume overload on the incidence of AF they found that increased fluid balance on the first or second postoperative days after cardiac surgery was an independent predictor of POAF 2425 Both studies hypothesized that volume overload will lead to left atrial dilation and thus predispose to AF However neither of the studies had recorded measurements of left atrial size
Few studies have investigated the intraoperative factors of POAF It is known that concurrent valve surgery increases the risk of POAF517 Other risk factors found consistently in the literature include cardiopulmonary bypass and aortic cross clamp times10151626 A multicenter study found that bicaval cannulation and pulmonary vein venting might be associated with increased risk of POAF 5 In addition an earlier retrospective study found that snared bicaval cannulation was associated with increased incidence of postoperative atrial arrhythmias in patients receiving high volume crystalloid cardioplegia However this effect was not observed when low volume cardioplegia was used to compare unsnared bicaval cannulation with cavoatrial cannulation9
It has been postulated that atrial incision and atrial ischemia during surgery lead to alterations of atrial conduction and refractoriness thereby predisposing to the development of POAF 10 In addition Tchervenkov et al found an association between persistence of residual atrial electrical activity during cardioplegic arrest and post-operative atrial tachyarrhythmia27 It might be that atrial activity during cardioplegic arrest -which could be due to inadequate atrial protection - resulted in atrial ischemia which in turn contributes to POAF development 27 It has been demonstrated that return of relatively warm venous blood to the right atrium and ventricle may lead to myocardial warming thereby diminishing the protective effect of cardioplegia Older animal studies have shown conflicting results regarding the optimal cannulation technique to reduce myocardial rewarming during arrest2829 Furthermore no study prospectively investigated the effect of different cannulation techniques on post-operative atrial tachyarrhythmia
Due to the scarcity of data regarding the intraoperative risk factors of POAF these factors are not well recognized and preventative strategies are therefore not well established
2 Objectives To estimate the proportion of eligible people who are willing to participate the number of participants who drop out of the trial and use the results of this study to inform a larger study
3 Study design 31 Recruitment and sample size Participants will be screened to enter the study in clinic by the principal investigator who is cardiac surgeon Only the principal investigators patients who meet inclusion criteria will be considered in the study Eligibility to enter the study will be determined during the patients consultation in clinic
Considering we usually operate on 1 or 2 patients per week who meet inclusion criteria We believe that 20 patients per group is reasonable to assess feasibility of recruitment and protocol implementation
32 Study population and study procedure
Patients admitted to the Jewish General Hospital for elective coronary artery bypass grafting from January 2021 will be included in the study Patients will be screened in clinic prior to admission The study population will include 40 patients that will be randomly assigned to one of two treatment groups according to the venous cannulation technique used during surgery Group A will undergo cavoatrial cannulation with a 2-stage venous cannula Group B will undergo bicaval cannulation with snares
33 Intervention Bicaval cannulation will be performed through in the right atrium Small tapes are passed around the SVC and IVC Two purse string sutures are placed in the superior and inferior portions of right atrium Two small incisions are made inside the purse string sutures The SVC and IVC are cannulated through the superior and inferior incisions respectively The purse string sutures and small tapes passed through small tubes and snared The small tapes snare will act as a tourniquet to prevent venous return to the right atrium Bicaval cannulation is performed in cases of mitral and tricuspid valve operations to provide a bloodless operative field superior drainage of venous blood and potentially better protection of the heart compared to cavoatrial cannulation Similar surgical methods will be used in all treatment groups We will use a standard sternotomy incision to access the heart the distal ascending aorta be will cannulated Antegrade Del Nido cardioplegia will be used to arrest the heart under normothermia The left internal mammary artery will be grafted to the left anterior descending artery For the other grafts the left radial artery and saphenous venous grafts will be used where appropriate The saphenous vein will be harvested endoscopically and the radial artery will be harvested using an open technique Pre-operative beta-blockers will be continued to the day of surgery and re-started on the first post-operative day if heart rate and blood pressure were permissible
34 Randomization and blinding Patients will be screened in clinic They will be blinded to their treatment and will be prospectively randomized on hospital admission by simple randomization using a random numbers table Randomization will be performed by the principal investigator
35 Study measurements Patients data including demographics number of diseased coronary arteries and comorbidities such as presence of hypertension chronic kidney disease diabetes mellitus peripheral vascular disease previous stroke or myocardial infarction will be collected Operative data including patients temperature cardiopulmonary bypass time cross-clamp time aortic and venous cannulation technique number and location of bypasses will also be collected Echocardiographic parameters will be collected preoperatively intra-operatively and post-operatively These will include left ventricular ejection fraction right ventricular function left and right atrial volume indices RV myocardial performance index MPI and the presence of valvular heart disease Postoperative data will include serum electrolytes cardiac biomarkers volume status and beta-blocker use Postoperative echocardiogram will be done between POD 3-5 and while the heart is in sinus rhythm and with a heart rate 100bpm whenever possible
38 Data reporting Baseline and demographic data will be summarized by standard descriptive summaries eg means and standard deviations for continuous variables and percentages for categorical variables Hypothesis testing will not be performed as this is a feasibility study and the sample size to too small to yield significant conclusions
4 Confidentiality Informed consent will be taken in clinic by the principal investigator during participants visit Participants will be informed that theyre able to withdraw from the study at anytime pre-operatively An additional consent form separate from the regular operation consent form will be used for the study
Data will be collected in a paper data collection form which will then be transferred to a secure excel document The excel document will be password protected Paper forms will be placed in a secure cabinet in a locked office Only members of the research team will have access to the electronic and paper forms
5 Risk Assessment The risks associated with bicaval cannulation are minimal There is potential for increased risk of bleeding because of the need for two incisions instead of one Since were cannulating the SVC and IVC indirectly through atrial incisions these potential bleeding sites can be easily seen and controlled intra-operatively
There is a possibility of increased incidence of atrial fibrillation post-operatively in the intervention group Although uncommon some surgeons routinely perform bicaval cannulation for CABG
Participants may benefit from the intervention if it leads to decreased rate of POAF Thus avoiding the potential sequelae of AF and the side effects of treatment
6 PUBLICATION We plan to use the data obtained in this study for publication in a peer-review journal We may present the findings of the study in scientific conferences No identifiable information will be published
Appendix A Consent form
Study Title Effect of venous cannulation technique on the incidence of post-operative atrial fibrillation in patients undergoing elective coronary artery bypass grafting A pilot randomized controlled trial
Principle investigators Jean-Francois Morin MD Husain Esmaeil MD Alex Alojko Study Site Jewish General Hospital Address 3755 Chemin de la Côte-Sainte-Catherine Montréal QC H3T 1E2 Telephone 514 340-8222
Introduction You are being asked to participate in a research study Before agreeing to participate it is important that you read the following explanation of this study
The decision to participate in this study is up to you Your participation is completely voluntary Your decision will not affect your relationship with your regular doctor or your current or future medical care
Please read this form carefully Feel free to discuss the study with your family friends and healthcare provider before you make your decision whether to participate Ask about anything you dont understand or would like explained better Take time to decide whether or not you want to take part in this study and ask the study doctor or study staff as many questions about the study as you would like
Background and purpose You are being asked to take part in this study because you have been diagnosed with coronary artery disease and will undergo coronary artery bypass grafting
Atrial fibrillation is a type of heart arrhythmia that occurs in about 30 of patients undergoing coronary artery bypass grafting This rhythm problem could cause a clot to form in the heart this clot can travel to brain and cause a stroke Atrial fibrillation is a treatable condition The treatment method depends on the clinical situation It is usually treated with medications that either controls the speed or the rhythm of the heart If the arrhythmia causes severe symptoms such as chest pain dizziness or hypotension low blood pressure it is sometimes treated with an electrical current called electrical cardioversion to restore the heart to its normal rhythm
During heart surgery the heart will be stopped in order to perform the coronary artery bypass surgery The heart will be connected to a heart-lung machine also called cardiopulmonary bypass machine This machine takes over the job of the heart and lungs A plastic tube will be connected to right upper chamber of the heart called the right atrium to the machine this tube is called the venous cannula the tube carries blood from the heart into an oxygenator where it will be oxygenated The oxygenated blood is pumped into the body through a tube connected to the aorta the bodys main blood vessel
Another method of the venous cannulation is by connecting two tubes to the superior vena cava and inferior vena cava the two major veins carrying blood returning from the body to the right atrium of the heart This is the same method used for mitral and tricuspid valve operations
The purpose of this study is to look into the effect of different venous cannulation methods on the occurrence of atrial fibrillation a type of arrhythmia post coronary artery bypass grafting This study has 2 groups You will be randomly assigned to one of the two groups The first group will have the venous cannula connected to the right atrium which is the standard method The second group will have the venous cannula connected to the superior and inferior vena cava and a tie is secured around the cannula so that no blood passes into the right atrium instead the blood goes to the heart-lung machine
Potential Risks
There are potential risks to you by taking part in this study The rate of occurrence of atrial fibrillation heart arrhythmia could be higher in the treatment group you are assigned to The bleeding risk is theoretically higher since we are making an incision in 2 areas to insert the cannulas instead of a single incision in the standard method If bleeding occurs you might need a blood transfusion or in uncommonly you might need to be re-operated on to control the bleeding In addition there are some risks inherent to the coronary artery bypass grafting surgery which include bleeding heart attack heart rhythm problems heart failure which is inadequate pumping of blood by the heart Depending on the cause of the heart attack It can be managed with medications going back to surgery or by coronary angioplasty and placing a stent Heart failure is treated with medications
Other potential risks of coronary artery bypass grafting include liver problems elevated liver enzymes due to inadequate blood supply during the operation kidney injury due to inadequate blood supply during the operation Liver and kidney complications are usually managed with monitoring of their functions
Other risks inherent to the surgery include lung problems such as lung infection fluid collecting in the lungs or inability to disconnect the ventilator machine after the operation due to inability of the lungs to oxygenate the blood on their own and other uncommon risks such as stroke and death
Potential Benefits
You may benefit as a result of your participation in this study The rate of atrial fibrillation could be lower in the treatment group you are assigned to However there is no assurance that you will benefit from your participation in this study Results from this study may benefit other patients in the future
Alternative Treatments
This clinical study is for research purposes only You do not have to participate in the study to receive treatment for coronary artery disease The other option is a standard venous cannulation method in which the right atrium is cannulated
Voluntary ParticipationWithdrawal Your decision to participate in this clinical research study is voluntary You may choose not to participate or you may withdraw from the study for any reason at any time without penalty You should tell the study doctor or study team if you decide to leave the study
The study doctor can stop the study or your participation in the study at any time without your consent if it appears to be medically harmful to you if the study is cancelled or for administrative reasons
Confidentiality As part of this research we will collect personal information from you this means information that can identify you In order to protect your privacy all information collected will remain confidential to the extent permitted by law Your identifiable health information is protected by a law If the results of this study are published or presented at meetings you will not be identified
For monitoring control protection and security purposes your research study file could be checked by persons authorized by the Research Ethics Committee of the CIUSSS du Centre-Ouest-de-lÎle de Montréal These persons are bound by a confidentiality agreement
For all questions concerning your rights during your participation in this study or if you have any complaints or comments regarding your experience in taking part in this research study you can contact the Local Commissioner of Complaints and Quality of Service of the CIUSSS Centre-Ouest-de-lÎle-de-Montréal or the ombudsman of the institution at 514 340-8222 ex 24222
STATEMENT OF CONSENT
Study title Effect of venous cannulation technique on the incidence of post-operative atrial fibrillation in patients undergoing elective coronary artery bypass grafting A pilot randomized controlled trial
PARTICIPANT STATEMENT
I understand the information that was explained to me as contained in this consent form All my questions were answered to my satisfaction I will receive a copy of this signed consent form My participation is voluntary and I can withdraw from the research study at any time without any consequences and without having to give a reason Withdrawing from this research study at any time will not affect my medical care now or later in any way By signing this consent form I do not give up any of my legal rights
I agree to participate in this research study
Name of Participant
Signature Date
RESEARCHER STATEMENT
I as the person obtaining consent certify that I have explained to the participant or hisher legal representative where applicable the research study information contained in this consent form and have answered all questions I have clearly explained to the participant that she is free to withdraw at any time without providing a reason and without any consequences I commit together with the members of the research team to respect all conditions described in this consent form and to give a signed copy of the consent form to the participant
Name and signature of the researcher or person delegated to obtained consent
Date
TranslatorWitness if applicable
Name and signature of translatorwitness Date
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None