Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04090905 |
| Other study ID # |
H-19033464 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 13, 2020 |
| Est. completion date |
December 31, 2021 |
Study information
| Verified date |
May 2022 |
| Source |
Frederiksberg University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Background and purpose Post-operative AF (POAF) is considered a phenomenon rather than a
definite diagnosis and the current clinical guidelines have no specific recommendations
regarding its management. Few prospective studies have been performed in non-cardiac
conditions and the consequences of POAF in patients without known heart disease are not well
described. However, recent data suggest an association between POAF in relation to
non-cardiac surgery and increased post-operative mortality and stroke. POAF in relation to
abdominal surgery seems common (incidence: 8-18%); however, the true incidence is uncertain.
The available studies are few, heterogeneous, and often methodologically inadequate. The
study aims at reporting the incidence of atrial fibrillation (AF), and associated
complications, in relation to abdominal surgery.
Material and methods Designed as a prospective, single-centre, cohort study of consecutive
adult patients undergoing acute* abdominal surgery at the Department of Abdominal Surgery at
Bispebjerg Hospital. Patients who are pregnant or where follow-up is not possible will be
excluded. Patients will be examined pre-operatively by ECG and signal processed surface ECG
(wavECG). A subset of patients admitted to the Department in the time interval of 7 AM to 11
PM$, will be offered heart rhythm monitoring from admission and until discharge (preferably
≥72 hours post-operatively). Additional follow-up will be based on a review of patient charts
at discharge and one# month postoperatively. The primary endpoint is the
occurrence/recurrence of AF. The study will include 400-500 patients of which an estimated
2/3 will wear heart rhythm monitoring corresponding to 264-330 patients.
Perspective If more thorough heart rhythm monitoring of patients undergoing abdominal surgery
leads to the identification of more patients with AF, routine continuous heart rhythm
monitoring should be considered recommended in upcoming guidelines to prevent associated
complications.
Footnote(s): See 'Detailed Description' below.
Description:
Background and rationale Post-operative AF (POAF), i.e. atrial fibrillation (AF) that occurs
secondarily to surgery is considered a phenomenon rather than a definite diagnosis, and
continuous anti-coagulation is not recommended in AF of short duration and non-persistent
AF.1,2 The most recent guidelines from the European and American Societies of Cardiology have
no specific recommendation regarding the management of secondary AF, though referral to an
outpatient cardiology clinic can be considered if the condition is not self-limiting.3,4
Despite this, recent data from the Framingham population suggest that secondary AF is not a
benign condition,5,6 and some studies have found POAF in relation to non-cardiac surgery to
be associated with increased post-operative mortality and stroke.7-9 Currently few
prospective studies have been performed in non-cardiac conditions and the consequences of
secondary AF in patients without known heart disease are not well described. POAF in relation
to non-cardiac surgery is common with an average incidence of 10.94%.10 However, the true
incidence of POAF in relation to non-cardiac surgery is uncertain, as the available studies
are few, heterogeneous, and often methodologically inadequate.10 Different
risk-stratification models exist, however it is still challenging to accurately predict which
patients will develop AF both perioperatively and in the years following surgery.11-14
Important risk factors for developing POAF are: age (age 65-74, OR 2.08; age >85, OR 3.56),
hypertension (OR 3.66), heart failure (OR 1.64), thyroid disease (OR 6.29), laparotomy vs
laparoscopy (OR 3.30) and duration of surgery (> 600 min, OR 1.38).10 The use of
electrocardiogram (ECG) in risk stratification for AF and stroke is not yet incorporated in
clinical guidelines. However, short and prolonged p-wave and p-wave terminal force in lead V1
(PTFV1) is correlated with AF.15 Myovista (HeartSciences, Southlake, Texas, USA) is a novel
ECG utilizing continuous wavelet transform signal processing (wavECG) and can be used to
prove left ventricular diastolic dysfunction (LVDD).16 LVDD is in other studies associated
with AF.17-20 These new biomarkers might improve the identification of patients at risk of
developing POAF.
Purpose The study aims at reporting the incidence of AF, and associated complications, in
relation to acute abdominal surgery. Concurrently, patients will be characterized by
specialized ECG analysis and wavECG.
Methods Prospective, single-centre, cohort study of consecutive patients undergoing acute*
abdominal surgery. Patients will be identified among acute referrals for the Department of
Abdominal Surgery at Bispebjerg-Frederiksberg Hospital. The Investigator (Department of
Cardiology at Bispebjerg-Frederiksberg Hospital) will ensure signed informed consent prior to
any study-related examinations. Surgery will be performed at the Department of Abdominal
Surgery at Bispebjerg-Frederiksberg Hospital independently of study enrolment. A subset of
patients will be enrolled in a feasibility study of continuous cardiac rhythm monitoring
(C3+, Cortrium, Copenhagen, Denmark). Heart rhythm monitoring will be worn from admission and
until discharge (preferably ≥72 hours post-operatively) in patients admitted to the
Department in the time interval of 7 AM to 11 PM$. Additional follow-up will be based on a
review of patient charts at discharge and one# month postoperatively.
No randomization or placebo will be used. ECG measurements will be compared to existing data
from a healthy population.
Measurements
- ECG: AF, PR-interval, p-wave area, PTFV1
- wavECG: LVDD
- Heart rhythm monitoring: AF
Statistical considerations Consecutive patients attending the Department of Abdominal Surgery
at Bispebjerg-Frederiksberg Hospital will be invited to participate in the pre- and
post-operative examination programme. The study's aim is to identify the incidence of peri-
and postoperative AF. Hence, sample size calculations are uncertain. The expected incidence
of AF for patients undergoing non-oesophageal abdominal surgery is at least 7.63%.10
Pre-operative p-wave indices have shown the ability to predict POAF in a cardiac surgery
population of 105 patients (with a POAF incidence of 11%).21 wavECG has been used to show
LVDD in a study population of 188 patients referred for computed tomography angiography of
the heart.16 The study will include 400-500 patients of which an estimated 2/3 will wear
heart rhythm monitoring corresponding to 264-330 patients. Follow-up will be one month.
Normality was inspected visually by histograms and tested by Shapiro-Wilk. Nonparametric
statistics were used. Wilcoxon rank-sum (continuous variables) and Chi-square and Fisher's
exact test (categorical variables) were used as appropriate. Data were presented as median
with interquartile range (IQR) for continuous variables and frequency with percentages for
categorical variables. Odds ratios (OR) with 95% confidence intervals (CI) were calculated
for dichotomous values by univariate logistic regression. Multiple logistic regression was
used to adjust for variables' influence on the primary outcome of POAF and the secondary
outcome of severe adverse events. Based on an á priori knowledge of risk factors of atrial
fibrillation and expected important surgical factors, variables were chosen for the full
multivariate model. The following variables were included: age, sex, prior atrial
fibrillation, prior stroke, hypertension, heart failure, heart valve disease, chronic renal
disease, diabetes mellitus, vascular disease, chronic obstructive pulmonary disease, cancer,
surgery invasiveness, and surgery urgency. For multivariate modeling of the secondary
outcome, POAF was added to the full model as it was expected to influence the development of
the outcome. Subsequently, the full multivariate logistic regression model was reduced to a
prediction model. Variables with p<0.05 remained in the prediction model, while variables
with p>0.05 were eliminated. Multicollinearity was checked and a Variance Inflation Factor
level <5 was accepted. McFadden's R-squared test was applied to evaluate model fit, while
Analysis of variance (ANOVA) tests were applied to compare the components of the model, to
reduce the risk of overfitting. A receiver operating characteristic curve (ROC) with area
under the curve (AUC) was calculated for the multivariate model. The Closest Topleft decision
rule was applied to define the optimal sensitivity and specificity values. For AUC,
sensitivity, and specificity, 95% confidence intervals were produced through bootstrapping
with 2000 replicates. All tests were two-sided, and a p< 0.05 was considered statistically
significant. RStudio (version 1.4.1717) was used for statistical analyses.
Footnote(s): *The study was originally designed to include both acute and elective patients,
but due to limited availability of heart rhythm monitoring devices, prior to study initiation
(June 5, 2020), we decided to enroll patients referred for acute abdominal surgery only. $The
study was originally planned to apply heart rhythm monitors all 24 hours of the day. This was
not possible due to logistics, and prior to study initiation, we agreed to apply monitoring
to all patients admitted between 7 AM to 11 PM. #The study was originally planned for 12
months follow-up but was reduced to one month, due to limitations of the permissions achieved
prior to study initiation. In addition, an outpatient clinic visit 3 months after surgery was
planned where ECG and heart rhythm monitor examinations were to be repeated. The visits were
canceled due to local COVID-19 restrictions.
