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Clinical evaluation and implications of left atrial remodeling in atrial fibrillation: From silent cerebral lesions and atrial stunning to novel electrocardiographic tools for prediction of arrhythmia outcome
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.ORCID iD: 0000-0002-2079-7446
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Left atrial (LA) remodeling and reverse remodeling are associated with cerebral involvement and cognitive function (CF) changes. Risk stratification for AF related outcomes is essential in the management of patients with AF. 

This thesis aimed to 1) explore the effects of AF in a prospective cohort of anticoagulant-naïve patients, who underwent cardioversion (CV) within 48 hours after debut (Studies I and II) on i) occurrence of new silent thromboembolic events using brain magnetic resonance imaging, CF, cerebral biomarker ii) atrial remodeling and thrombogenicity using echocardiography, and hypercoagulability biomarkers; 2) identify novel electrocardiographic (ECG) predictors of 12-months AF recurrence, (Study III), in patients with non-permanent AF after CV or pulmonary vein isolation and study its effect on reverse atrial electrical remodeling (RAER) and 3) to evaluate traditional and novel ECG- and clinical predictors of new-onset AF (new-o-AF) on hospitalized Covid-19 patients (Study IV)  and explore the impact of AF on clinical outcomes.

In Papers I and II, acute silent cerebral lesions could not be identified. A higher incidence of white matter hyperintensities was associated with higher CHA2DS2-VASc-score. A transient increase in cerebral damage biomarker was observed. Persistent AF patients had inferior CF test results. LA stunning resolved within ten days. The reverse functional remodeling was incomplete in patients with AF history. Higher levels of hypercoagulability-related biomarkers were observed prior to CV. 

In Paper III, the novel Peq-time>33ms, from P-wave onset to the peak positive deflection, independently predicted 12-months AF recurrence. The P-leftward-area, from peak positive deflection to the offset of P-wave, showed the largest change during follow-up, describing RAER. Machine-learning predictive model including variables from the novel P-wave partitioning showed the best predictive performance.

In Paper IV, the novel Peq-time>33ms, PR-interval>190ms and P-wave-duration>115ms were independent predictors of n-o-AF. Admission to the intensive care unit (ICU), need for respiratory support, advanced age, males and increased body mass index (BMI) independently predicted new-o-AF. Logistic regression predictive models including age, sex, BMI, ICU admission and Peq-time or PR-interval had the best balanced accuracy.

In conclusion, our findings in Studies I and II might suggest an enhanced thrombogenicity, even in patients with low stroke risk, supporting the concept of anticoagulation pericardioversion. We introduced the novel Peq-time, independently predicting AF recurrence in Study III and, along with PR-interval, new-o-AF in Study IV. Predictive models of arrhythmia outcome could be implemented in individually-tailored AF management and surveillance.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2023. , p. 92
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1949
Keywords [en]
Atrial fibrillation, left atrial remodeling, recurrence, new-onset, silent cerebral lesions, white matter hyperintensities, cardioversion, pulmonary vein isolation, risk factors, electrocardiographic predictors, P-wave indices, machine learning, predictive models, Covid-19
National Category
Cardiology and Cardiovascular Disease
Identifiers
URN: urn:nbn:se:uu:diva-500683ISBN: 978-91-513-1816-5 (print)OAI: oai:DiVA.org:uu-500683DiVA, id: diva2:1752602
Public defence
2023-06-14, H:son Holmdahlsalen, Akademiska sjukhuset, ingång 100, Dag Hammarskjölds Väg 8, Uppsala, 08:00 (English)
Opponent
Supervisors
Available from: 2023-05-24 Created: 2023-04-24 Last updated: 2025-02-10
List of papers
1. Serial Magnetic Resonance Imaging after Electrical Cardioversion of Recent Onset Atrial Fibrillation in Anticoagulant-Naïve Patients –: A Prospective Study Exploring Clinically Silent Cerebral Lesions
Open this publication in new window or tab >>Serial Magnetic Resonance Imaging after Electrical Cardioversion of Recent Onset Atrial Fibrillation in Anticoagulant-Naïve Patients –: A Prospective Study Exploring Clinically Silent Cerebral Lesions
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2020 (English)In: Journal of Atrial Fibrillation, ISSN 1941-6911, Vol. 13, no 2Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Cardiofront, 2020
Keywords
Silent brain lesions, Atrial fibrillation, Cognitive function, Cardioversion.
National Category
Cardiology and Cardiovascular Disease
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-429683 (URN)
Available from: 2021-01-01 Created: 2021-01-01 Last updated: 2025-02-10Bibliographically approved
2. Recent-onset atrial fibrillation: a study exploring the elements of Virchow's triad after cardioversion
Open this publication in new window or tab >>Recent-onset atrial fibrillation: a study exploring the elements of Virchow's triad after cardioversion
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2022 (English)In: Journal of Interventional Cardiac Electrophysiology, ISSN 1383-875X, E-ISSN 1572-8595, Vol. 64, no 1, p. 49-58Article in journal (Refereed) Published
Abstract [en]

Purpose

Atrial fibrillation (AF) imposes an inherent risk for stroke and silent cerebral emboli, partly related to left atrial (LA) remodeling and activation of inflammatory and coagulation systems. The aim was to explore the effects of cardioversion (CV) and short-lasting AF on left atrial hemodynamics, inflammatory, coagulative and cardiac biomarkers, and the association between LA functional recovery and the presence of a prior history of AF.

Methods

Patients referred for CV within 48 h after AF onset were prospectively included. Echocardiography and blood sampling were performed immediately prior, 1–3 h after, and at 7–10 days after CV. The presence of chronic white matter hyperintensities (WMH) on magnetic resonance imaging was related to biomarker levels.

Results

Forty-three patients (84% males), aged 55±9.6 years, with median CHA2DS2-VASc score 1 (IQR 0–1) were included. The LA emptying fraction (LAEF), LA peak longitudinal strain during reservoir, conduit, and contractile phases improved significantly after CV. Only LAEF normalized within 10 days. Interleukin-6, high-sensitivity cardiac-troponin-T (hs-cTNT), N-terminal-pro-brain-natriuretic peptide, prothrombin-fragment 1+2 (PTf1+2), and fibrinogen decreased significantly after CV. There was a trend towards higher C-reactive protein, hs-cTNT, and PTf1+2 levels in patients with WMH (n=21) compared to those without (n=22). At 7–10 days, the LAEF was significantly lower in patients with a prior history of AF versus those without.

Conclusion

Although LA stunning resolved within 10 days, LAEF remained significantly lower in patients with a prior history of AF versus those without. Inflammatory and coagulative biomarkers were higher before CV, but subsided after 7–10 days, which altogether might suggest an enhanced thrombogenicity, even in these low-risk patients.

Keywords
Physiology: medical, Cardiology, Cardiovascular Medicine
National Category
Cardiology and Cardiovascular Disease
Research subject
Cardiology
Identifiers
urn:nbn:se:uu:diva-456899 (URN)10.1007/s10840-021-01078-9 (DOI)000710619700001 ()34689250 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research CouncilErik, Karin och Gösta Selanders FoundationUppsala University
Available from: 2021-10-24 Created: 2021-10-24 Last updated: 2025-02-10Bibliographically approved
3. Novel P-wave indices and machine learning predict atrial fibrillation recurrence after rhythm control interventions
Open this publication in new window or tab >>Novel P-wave indices and machine learning predict atrial fibrillation recurrence after rhythm control interventions
(English)Manuscript (preprint) (Other academic)
Keywords
Atrial fibrillation, Atrial fibrillation recurrence, P-wave indices, Pulmonary vein isolation, Cardioversion, Machine learning
National Category
Cardiology and Cardiovascular Disease
Identifiers
urn:nbn:se:uu:diva-500678 (URN)
Available from: 2023-04-21 Created: 2023-04-21 Last updated: 2025-02-10
4. Risk factors and electrocardiographic predictors associated with new-onset atrial fibrillation in hospitalized Covid-19 patients. Evaluation of a novel P-wave index.
Open this publication in new window or tab >>Risk factors and electrocardiographic predictors associated with new-onset atrial fibrillation in hospitalized Covid-19 patients. Evaluation of a novel P-wave index.
Show others...
(English)Manuscript (preprint) (Other academic)
Keywords
New-onset atrial fibrillation, Covid-19, Risk factors, Electrocardiographic predictors, P-wave indices, Logistic regression predictive model
National Category
Cardiology and Cardiovascular Disease
Identifiers
urn:nbn:se:uu:diva-500681 (URN)
Available from: 2023-04-21 Created: 2023-04-21 Last updated: 2025-02-10

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