Effect of Continuous Electrocardiogram Monitoring on Detection of Undiagnosed Atrial Fibrillation After Hospitalization for Cardiac Surgery: A Randomized Clinical Trial

Abstract

Importance: Postoperative atrial fibrillation (POAF) occurring after cardiac surgery is associated with adverse outcomes. Whether POAF persists beyond discharge is not well defined.

Objective: To determine whether continuous cardiac rhythm monitoring enhances detection of POAF among cardiac surgical patients during the first 30 days after hospital discharge compared with usual care.

Design, setting, and participants: This study is an investigator-initiated, open-label, multicenter, randomized clinical trial conducted at 10 Canadian centers. Enrollment spanned from March 2017 to March 2020, with follow-up through September 11, 2020. As a result of the COVID-19 pandemic, enrollment stopped on July 17, 2020, at which point 85% of the proposed sample size was enrolled. Cardiac surgical patients with CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex) score greater than or equal to 4 or greater than or equal to 2 with risk factors for POAF, no history of preoperative AF, and POAF lasting less than 24 hours during hospitalization were enrolled.

Interventions: The intervention group underwent continuous cardiac rhythm monitoring with wearable, patch-based monitors for 30 days after randomization. Monitoring was not mandated in the usual care group within 30 days after randomization.

Main outcomes and measures: The primary outcome was cumulative AF and/or atrial flutter lasting 6 minutes or longer detected by continuous cardiac rhythm monitoring or by a 12-lead electrocardiogram within 30 days of randomization. Prespecified secondary outcomes included cumulative AF lasting 6 hours or longer and 24 hours or longer within 30 days of randomization, death, myocardial infarction, ischemic stroke, non-central nervous system thromboembolism, major bleeding, and oral anticoagulation prescription.

Results: Of the 336 patients randomized (163 patients in the intervention group and 173 patients in the usual care group; mean [SD] age, 67.4 [8.1] years; 73 women [21.7%]; median [interquartile range] CHA2DS2-VASc score, 4.0 [3.0-4.0] points), 307 (91.4%) completed the trial. In the intent-to-treat analysis, the primary end point occurred in 32 patients (19.6%) in the intervention group vs 3 patients (1.7%) in the usual care group (absolute difference, 17.9%; 95% CI, 11.5%-24.3%; P < .001). AF lasting 6 hours or longer was detected in 14 patients (8.6%) in the intervention group vs 0 patients in the usual care group (absolute difference, 8.6%; 95% CI, 4.3%-12.9%; P < .001).

Conclusions and relevance: In post-cardiac surgical patients at high risk of stroke, no preoperative AF history, and AF lasting less than 24 hours during hospitalization, continuous monitoring revealed a significant increase in the rate of POAF after discharge that would otherwise not be detected by usual care. Studies are needed to examine whether these patients will benefit from oral anticoagulation therapy.

Trial registration: ClinicalTrials.gov Identifier: NCT02793895.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Ha reported receiving lecture fees from Bayer, Bristol Myers Squibb/Pfizer, and Servier. Dr S. Verma reported holding a Tier 1 Canada Research Chair in Cardiovascular Surgery; reported receiving research grants and speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, EOCI Pharmacomm, Ltd, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio, Sanofi, Sun Pharmaceuticals, and the Toronto Knowledge Translation Working Group; and reported being the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. Dr Mazer reported receiving advisory board fees from Amgen, AstraZeneca, Boehringer Ingelheim, and Octapharma. Dr Jacques reported receiving nonfinancial support from Medtronic and Icentia, grants and nonfinancial support from Allergan and Abbvie, and personal fees from LivaNova. Dr Deyell reported receiving personal fees from Medtronic and Servier. Ms Wilson reported receiving personal fees from HLS Therapeutics and Pfizer. Dr H. Teoh reported receiving honoraria from Boehringer Ingelheim and HLS Therapeutics. Dr Jüni reported serving as an unpaid steering committee member for Astra Zeneca, Biotronik, Biosensors, Abbott, and the Medicines Company, and reported receiving consulting fees from Amgen, Ava, and Fresenius. Dr Bhatt reported receiving advisory board fees from Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Regado Biosciences; being a member of the Board of Directors for the Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; being inaugural chair for the American Heart Association Quality Oversight Committee; serving on data monitoring committees for Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), and Population Health Research Institute; receiving honoraria from the American College of Cardiology (ACC; senior associate editor of Clinical Trials and News and chair of the ACC accreditation oversight committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor and associate editor), K2P (cochair, interdisciplinary curriculum), Level Ex (continuing medical education steering committees), Medtelligence/ReachMD, MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national coleader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary and treasurer), and WebMD (continuing medical education steering committees); being deputy editor of Clinical Cardiology, chair of the NCDR-ACTION Registry Steering Committee, and chair of the VA CART Research and Publications Committee; receiving grant support from Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Lexicon, Lilly, Medtronic, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company, and 89Bio; receiving royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); being a co–site investigator for Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Philips, and Svelte; being a trustee for the ACC; and conducting unfunded research with FlowCo, Merck, and Takeda. Dr A. Verma reported receiving grant support from Biotronik, Bristol Myers Squibb, and Boehringer Ingelheim; receiving grant support, advisory board fees, and lecture fees from Bayer and Biosense Webster; receiving advisory board fees and lecture fees and serving as principal investigator (PULSED AF and DIAMOND II trial) from Medtronic; receiving consulting fees for serving on steering committees for Boston Scientific, Kardium, Medlumics, and Thermedical; and receiving lecture fees from Servier. No other disclosures were reported.

Figures

Figure 1.. Randomization and Patients in the Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation (SEARCH-AF) Trial

A total of 2803 patients were screened for the study and 336 patients underwent randomization. In the group that was assigned to receive continuous monitoring, 8 patients did not undergo any monitoring and 2 patients completed the monitoring but the data were not received by the monitoring center. In the usual care group, no patient underwent continuous monitoring and 4 patients underwent non–protocol-mandated Holter monitoring. During follow-up, 6 patients withdrew consent in both groups. There were 6 and 11 patients who were lost to follow-up in the intervention and usual care group, respectively. A total of 163 patients in the monitoring group and 173 patients in the usual care group were included in the primary analysis. A detailed list of reasons for screen failure is provided in eTable 3 in Supplement 2. CHA2DS2-VASc indicates congestive heart failure, hypertension, age 75 years or older, diabetes, prior stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and female sex.

Figure 2.. Time to First Event Curves for the Primary End Point

Kaplan-Meier estimates of detection of cumulative atrial fibrillation (AF) or atrial flutter (AFL) lasting 6 minutes or longer or documentation of AF or AFL by a single 12-lead electrocardiogram within 30 days after randomization. The primary end point occurred in 32 patients (19.6%) in the monitoring group and in 3 patients (1.7%) in the usual care group for an absolute difference of 17.9% (95% CI, 11.5%-24.3%; P < .001).

Figure 3.. Cumulative Duration of Detected Atrial Fibrillation (AF) or Atrial Flutter (AFL) Episodes (per Patient) Within the First 30 Days of Randomization

Box and whisker plots of the cumulative duration of detected AF or AFL durations for patients randomized to continuous cardiac rhythm monitoring within the first 30 days of randomization. The upper and lower ends of the box represent the first and third quartile. The line in the box represents the median. In week 2, the median was 0.2 minutes. In week 1, the whisker above the upper quartile is drawn up to the largest observed point that falls within 1.5 times of the interquartile range (IQR). In week 2, the whisker is 1.5 times of the IQR. The whiskers below the lower quartile are not illustrated because they cross zero. Outliers are presented as circles located outside the whiskers. There were 10 patients who had AF lasting 6 minutes or longer in multiple monitoring weeks.