|
1
|
Sbrollini A, Rivolta MW, Van Dam P, Viani E, Morettini M, Sassi R, Burattini L, Locati ET. F-wave sway in paroxysmal and chronic atrial fibrillation. J Electrocardiol 2025; 90:153933. [PMID: 40245676 DOI: 10.1016/j.jelectrocard.2025.153933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 03/28/2025] [Accepted: 04/04/2025] [Indexed: 04/19/2025]
Abstract
Vectorcardiography (VCG) can evaluate the vector loops of electrocardiographic waves, being a time-spatial representation of the heart vector into the three orthonormal leads. During atrial fibrillation (AF), F waves reflect the disorganized depolarization of the atria, replacing the organized P wave. Usually, paroxysmal AF (PAF) spontaneously terminates, differently from chronic AF (CAF), possibly due to the still-preserved main direction of the P-wave vector loop. To investigate this hypothesis, this study aims to evaluate the similarities between the P-wave vector loop and F-wave vector sway in subjects affected by PAF and CAF. Overall, 10-s VCG were acquired from 10 healthy (HEA) subjects showing normal sinus rhythm, 10 subjects affected by PAF (one during normal sinus rhythm and one during AF), and 10 subjects affected by CAF. P waves were extracted using ECGdeli software, while F waves were extracted after QRST cancellation. Ellipse axes and eccentricities were calculated as the root mean square of VCG components and the ratio between axes, respectively. Overall, 84 beats of HEA, 205 beats of PAF (89 beats during normal sinus rhythm and 116 during fibrillation), and 103 beats of CAF were analyzed. Distributions of axes and eccentricities of PAF are not statistically different (P-value>0.05) than normal sinus rhythm but features related to the Z axis of CAF were statistically lower than PAF (P-value〈10-3). F-wave vector sway in PAF resembles the P-wave vector loop, suggesting the maintenance of the atrial depolarization main direction in subjects with self-terminating AF. Moreover, the F-wave vector sway is more manifest in PAF than in CAF.
Collapse
Affiliation(s)
- Agnese Sbrollini
- Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy
| | - Massimo W Rivolta
- Dipartimento di Informatica, Università degli Studi di Milano, Milan, Italy
| | - Peter Van Dam
- Center for Digital Medicine and Robotics, Jagiellonian University Medical College, Krakow, Poland
| | | | - Micaela Morettini
- Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy
| | - Roberto Sassi
- Dipartimento di Informatica, Università degli Studi di Milano, Milan, Italy
| | - Laura Burattini
- Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy.
| | - Emanuela T Locati
- Studio Cardiologico Locati, Milan, Italy; Department of Arrhythmology and Electrophysiology, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy
| |
Collapse
|
|
2
|
Somuncu MU, Güdül NE, Köktürk U, Köksal BG, Tatar FP, Avci A. Relationship between sST2 and NT-proBNP levels and postoperative atrial fibrillation in patients having non-cardiac surgery. Minerva Cardiol Angiol 2025; 73:192-200. [PMID: 39535528 DOI: 10.23736/s2724-5683.24.06649-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
BACKGROUND We explored the link between sST2 and NT-proBNP levels and postoperative atrial fibrillation (POAF) incidence in non-cardiac surgery patients in this study. METHODS The research involved 302 participants over 40 years old who underwent medium and/or high-risk non-cardiac surgeries. These patients were divided into two groups: those who developed POAF and those who did not. RESULTS The study cohort consisted of a total of 302 patients, with 14 (4.6%) experiencing POAF. POAF was more common in patients with previous heart failure, a high Left Atrial Volume Index (LAVI), and elevated ASA and RCRI scores (all P<0.05). LAVI, sST2, NT-proBNP, and RCRI scores were found to be independent predictors of POAF in patients undergoing non-cardiac surgeries (all P<0.05). The area under the curve (AUC) for sST2 and NT-proBNP in predicting POAF was 0.707 (95% CI 0.544-0.869; P=0.009) and 0.727 (95% CI 0.598-0.857; P=0.004), respectively. Combined elevation of sST2 and NT-proBNP increased the likelihood of developing POAF by approximately 8.5 times (OR: 8.65, CI 95% 1.06-35.3, P=0.044). CONCLUSIONS sST2 and NT-proBNP are valuable predictors of POAF in patients undergoing non-cardiac surgery. Identifying these predictors can help in recognizing high-risk patient groups for POAF.
Collapse
Affiliation(s)
- Mustafa U Somuncu
- Department of Cardiology, Faculty of Medicine, Aydın Adnan Menderes University, Aydın, Türkiye
| | - Naile E Güdül
- Department of Cardiology, Faculty of Medicine, Zonguldak Bülent Ecevit University, Zonguldak, Türkiye
| | - Uğur Köktürk
- Department of Cardiology, Faculty of Medicine, Zonguldak Bülent Ecevit University, Zonguldak, Türkiye -
| | - Bengü G Köksal
- Department of Anesthesia and Reanimation, Faculty of Medicine, Zonguldak Bülent Ecevit University, Zonguldak, Türkiye
| | - Fatih P Tatar
- Department of Cardiology, Faculty of Medicine, Zonguldak Bülent Ecevit University, Zonguldak, Türkiye
| | - Ahmet Avci
- Department of Cardiology, Faculty of Medicine, Zonguldak Bülent Ecevit University, Zonguldak, Türkiye
| |
Collapse
|
|
3
|
Brascia D, Mangiameli G, Giudici VM, Re Cecconi E, Luppichini M, Marulli G. Does the surgical approach affect the incidence of postoperative atrial fibrillation after thoracic surgery? A systematic review and meta-analysis. Updates Surg 2025:10.1007/s13304-025-02164-7. [PMID: 40082340 DOI: 10.1007/s13304-025-02164-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 03/03/2025] [Indexed: 03/16/2025]
Abstract
Postoperative atrial fibrillation (PAF) is a common complication after lung resection, since surgical stress may act as a trigger. The VATS approach reduces surgical stress and alleviates inflammation and oxidative stress commonly associated with open lung surgery. However, only a few studies have investigated the possible impact of the surgical approach on the incidence of PAF. A literature review was performed through PubMed, EMBASE, and Google Scholar in March 2024, to identify any study published since 2000 evaluating the role of the VATS vs the open approach to perform lung resections as a risk factor for postoperative atrial fibrillation. Pooled odds ratio (OR) estimates with 95% confidence intervals (CIs) were calculated. Twenty-one studies, including 59,101 patients, met the criteria for inclusion. Both propensity-matched and non-matched data showed that VATS was associated with a significant reduction in PAF compared to open thoracotomy (OT) (OR 0.73; 95% CI 0.58-0.91; I2 = 10.1%, p = 0.349). A meta-regression was conducted to explore contributing factors, showing the geographic regions in which the studies were conducted may be a significant source of heterogeneity. Subgroup analyses revealed less heterogeneity in studies conducted in Europe and on those focused solely on lobectomy. Postoperative atrial fibrillation risk following VATS is significantly lower than OT. Further prospective randomized controlled trials with large sample sizes are needed to confirm these findings.
Collapse
Affiliation(s)
- Debora Brascia
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4Pieve Emanuele, 20072, Milan, Italy
- Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Giuseppe Mangiameli
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4Pieve Emanuele, 20072, Milan, Italy
- Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Veronica Maria Giudici
- Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Emanuela Re Cecconi
- Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Matilde Luppichini
- Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Giuseppe Marulli
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4Pieve Emanuele, 20072, Milan, Italy.
- Division of Thoracic Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy.
| |
Collapse
|
|
4
|
Chen C, Wang G, Zou Q, Xiong K, Chen Z, Shao B, Liu Y, Xie D, Ji Y. m 6A reader YTHDF2 governs the onset of atrial fibrillation by modulating Cacna1c translation. SCIENCE CHINA. LIFE SCIENCES 2025; 68:706-721. [PMID: 39432207 DOI: 10.1007/s11427-024-2674-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 07/02/2024] [Indexed: 10/22/2024]
Abstract
Atrial fibrillation (AF) is the most common arrhythmia, which is tightly associated with the abnormal expression and function of ion channels in the atrial cardiomyocytes. N6-methyladenosine (m6A), a widespread chemical modification in eukaryotic mRNA, is known to play a significant regulatory role in the pathogenesis of heart disease. However, the significance of m6A regulatory proteins in the onset of AF remains unclear. Here, we demonstrate that the m6A reader protein YTHDF2 regulates atrial electrical remodeling and AF onset by modulating the Cav1.2 expression. Firstly, YTHDF2 expression was selectively upregulated in rat atrial cardiomyocytes with AF. Secondly, YTHDF2 knockout reduced AF susceptibility in mice. Thirdly, the knockout of YTHDF2 increased Cav1.2 protein levels in an m6A-in-dependent manner, ultimately prolonging the atrial myocardial refractory period, a critical electrophysiological substrate for the onset of AF. Fourthly, the N-terminal domain of YTHDF2 was identified as critical for Cacna1c mRNA translation regulation. Overall, our findings unveil that YTHDF2 can alter Cav1.2 protein expression in an m6A-independent manner, thereby facilitating the onset of AF. Our study suggests that YTHDF2 may be a potential intervention target for AF.
Collapse
Affiliation(s)
- Chuansheng Chen
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Guanghua Wang
- State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China
- Department of Pathology and Pathophysiology, School of Medicine, Tongji University, Shanghai, 200092, China
- Department of Cardiology, School of Medicine, Tongji University, Shanghai, 200120, China
| | - Qicheng Zou
- State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China
- Department of Cardiology, School of Medicine, Tongji University, Shanghai, 200120, China
| | - Ke Xiong
- State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China
- Department of Cardiology, School of Medicine, Tongji University, Shanghai, 200120, China
| | - Zhiwen Chen
- State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China
- Department of Pathology and Pathophysiology, School of Medicine, Tongji University, Shanghai, 200092, China
- Department of Cardiology, School of Medicine, Tongji University, Shanghai, 200120, China
| | - Beihua Shao
- State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China
- Department of Pathology and Pathophysiology, School of Medicine, Tongji University, Shanghai, 200092, China
- Department of Cardiology, School of Medicine, Tongji University, Shanghai, 200120, China
| | - Yi Liu
- State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China
- Department of Cardiology, School of Medicine, Tongji University, Shanghai, 200120, China
- Shanghai Arrhythmia Research Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China
| | - Duanyang Xie
- State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
- Department of Pathology and Pathophysiology, School of Medicine, Tongji University, Shanghai, 200092, China.
- Department of Cardiology, School of Medicine, Tongji University, Shanghai, 200120, China.
- Shanghai Arrhythmia Research Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
| | - Yong Ji
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing, 211166, China.
| |
Collapse
|
|
5
|
Kwon OC, Han K, Park MC. Risk of atrial fibrillation in patients with systemic sclerosis: a nationwide population-based study. Rheumatology (Oxford) 2024; 63:2838-2845. [PMID: 38048606 DOI: 10.1093/rheumatology/kead651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 10/24/2023] [Accepted: 11/19/2023] [Indexed: 12/06/2023] Open
Abstract
OBJECTIVE Atrial fibrillation (AF) is the most common arrhythmia in the general population, causing substantial economic burden, morbidity and mortality. The incidence rate and risk of AF in patients with SSc are unclear. We aimed to assess the incidence rate of AF in patients with SSc and the risk of incident AF in patients with SSc compared with the general population. METHODS The Korean National Health Insurance Service database was used as the data source. Patients with claims data for SSc between 2010 and 2017 were extracted from the database along with 1:5 age- and sex-matched controls. The index date was the earliest date with claims data for SSc between 2010 and 2017. The follow-up duration was from the index date to 2019. Multivariable Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95% CI for AF in patients with SSc. RESULTS Overall, 2519 patients with SSc and 12 595 age- and sex-matched controls were included. Over a mean follow-up duration of 5.2 years (s.d. 2.6), the incidence rates of AF were 3.52 and 1.68 per 1000 person-years for patients with SSc and controls, respectively. Compared with controls, patients with SSc had a significantly higher risk of incident AF [adjusted HR 2.095 (95% CI 1.466, 2.994)]. CONCLUSION Patients with SSc had a 2-fold higher risk of incident AF than controls. Given the significant economic burden, morbidity and mortality that AF poses, close monitoring for incident AF in patients with SSc is warranted.
Collapse
Affiliation(s)
- Oh Chan Kwon
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
| | - Min-Chan Park
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| |
Collapse
|
|
6
|
Iwamiya S, Ihara K, Nitta G, Sasano T. Atrial Fibrillation and Underlying Structural and Electrophysiological Heterogeneity. Int J Mol Sci 2024; 25:10193. [PMID: 39337682 PMCID: PMC11432636 DOI: 10.3390/ijms251810193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/16/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
As atrial fibrillation (AF) progresses from initial paroxysmal episodes to the persistent phase, maintaining sinus rhythm for an extended period through pharmacotherapy and catheter ablation becomes difficult. A major cause of the deteriorated treatment outcome is the atrial structural and electrophysiological heterogeneity, which AF itself can exacerbate. This heterogeneity exists or manifests in various dimensions, including anatomically segmental structural features, the distribution of histological fibrosis and the autonomic nervous system, sarcolemmal ion channels, and electrophysiological properties. All these types of heterogeneity are closely related to the development of AF. Recognizing the heterogeneity provides a valuable approach to comprehending the underlying mechanisms in the complex excitatory patterns of AF and the determining factors that govern the seemingly chaotic propagation. Furthermore, substrate modification based on heterogeneity is a potential therapeutic strategy. This review aims to consolidate the current knowledge on structural and electrophysiological atrial heterogeneity and its relation to the pathogenesis of AF, drawing insights from clinical studies, animal and cell experiments, molecular basis, and computer-based approaches, to advance our understanding of the pathophysiology and management of AF.
Collapse
Affiliation(s)
- Satoshi Iwamiya
- Department of Cardiovascular Medicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
| | - Kensuke Ihara
- Department of Cardiovascular Medicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
| | - Giichi Nitta
- Department of Cardiovascular Medicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
| | - Tetsuo Sasano
- Department of Cardiovascular Medicine, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
| |
Collapse
|
|
7
|
Apostolos A, Tsiachris D, Drakopoulou M, Trantalis G, Oikonomou G, Ktenopoulos N, Simopoulou C, Katsaros O, Tsalamandris S, Aggeli C, Tsivgoulis G, Tsioufis C, Toutouzas K. Atrial Fibrillation After Patent Foramen Ovale Closure: Incidence, Pathophysiology, and Management. J Am Heart Assoc 2024; 13:e034249. [PMID: 38639354 PMCID: PMC11179870 DOI: 10.1161/jaha.124.034249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Accepted: 02/06/2024] [Indexed: 04/20/2024]
Abstract
This comprehensive review explores the incidence, pathophysiology, and management of atrial fibrillation (AF) following percutaneous closure of patent foramen ovale (PFO). Although AF is considered a common adverse event post PFO closure, its incidence, estimated at <5%, varies based on monitoring methods. The review delves into the challenging task of precisely estimating AF incidence, given subclinical AF and diverse diagnostic approaches. Notably, a temporal pattern emerges, with peak incidence around the 14th day after closure and a subsequent decline after the 45th day, mimicking general population AF trends. The pathophysiological mechanisms behind post PFO closure AF remain elusive, with proposed factors including local irritation, device-related interference, tissue stretch, and nickel hypersensitivity. Management considerations encompass rhythm control, with flecainide showing promise, and anticoagulation tailored to individual risk profiles. The authors advocate for a personalized approach, weighing factors like age, comorbidities, and device characteristics. Notably, postclosure AF is generally considered benign, often resolving spontaneously within 45 days, minimizing thromboembolic risks. Further studies are required to refine understanding and provide evidence-based guidelines.
Collapse
Affiliation(s)
- Anastasios Apostolos
- First Department of Cardiology, Medical SchoolNational and Kapodistrian University of Athens, Hippokration General HospitalAthensGreece
| | - Dimitrios Tsiachris
- First Department of Cardiology, Medical SchoolNational and Kapodistrian University of Athens, Hippokration General HospitalAthensGreece
| | - Maria Drakopoulou
- First Department of Cardiology, Medical SchoolNational and Kapodistrian University of Athens, Hippokration General HospitalAthensGreece
| | - Georgios Trantalis
- First Department of Cardiology, Medical SchoolNational and Kapodistrian University of Athens, Hippokration General HospitalAthensGreece
| | - Georgios Oikonomou
- First Department of Cardiology, Medical SchoolNational and Kapodistrian University of Athens, Hippokration General HospitalAthensGreece
| | - Nikolaos Ktenopoulos
- First Department of Cardiology, Medical SchoolNational and Kapodistrian University of Athens, Hippokration General HospitalAthensGreece
| | - Chrysavgi Simopoulou
- First Department of Cardiology, Medical SchoolNational and Kapodistrian University of Athens, Hippokration General HospitalAthensGreece
| | - Odysseas Katsaros
- First Department of Cardiology, Medical SchoolNational and Kapodistrian University of Athens, Hippokration General HospitalAthensGreece
| | - Sotirios Tsalamandris
- First Department of Cardiology, Medical SchoolNational and Kapodistrian University of Athens, Hippokration General HospitalAthensGreece
| | - Constantina Aggeli
- First Department of Cardiology, Medical SchoolNational and Kapodistrian University of Athens, Hippokration General HospitalAthensGreece
| | - Georgios Tsivgoulis
- Second Department of Neurology, Medical SchoolNational and Kapodistrian University of Athens, Attikon University Hospital of AthensAthensGreece
| | - Costas Tsioufis
- First Department of Cardiology, Medical SchoolNational and Kapodistrian University of Athens, Hippokration General HospitalAthensGreece
| | - Konstantinos Toutouzas
- First Department of Cardiology, Medical SchoolNational and Kapodistrian University of Athens, Hippokration General HospitalAthensGreece
| |
Collapse
|
|
8
|
Halonen J, Kärkkäinen J, Jäntti H, Martikainen T, Valtola A, Ellam S, Väliaho E, Santala E, Räsänen J, Juutilainen A, Mahlamäki V, Vasankari S, Vasankari T, Hartikainen J. Prevention of Atrial Fibrillation After Cardiac Surgery: A Review of Literature and Comparison of Different Treatment Modalities. Cardiol Rev 2024; 32:248-256. [PMID: 36729126 DOI: 10.1097/crd.0000000000000499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Atrial fibrillation is the most common arrhythmia to occur after cardiac surgery, with an incidence of 10% to 50%. It is associated with postoperative complications including increased risk of stroke, prolonged hospital stays and increased costs. Despite new insights into the mechanisms of atrial fibrillation, no specific etiologic factor has been identified as the sole perpetrator of the arrhythmia. Current evidence suggests that the pathophysiology of atrial fibrillation in general, as well as after cardiac surgery, is multifactorial. Studies have also shown that new-onset postoperative atrial fibrillation following cardiac surgery is associated with a higher risk of short-term and long-term mortality. Furthermore, it has been demonstrated that prophylactic medical therapy decreases the incidence of postoperative atrial fibrillation after cardiac surgery. Of note, the incidence of postoperative atrial fibrillation has not changed during the last decades despite the numerous preventive strategies and operative techniques proposed, although the perioperative and postoperative care of cardiac patients as such has improved.
Collapse
Affiliation(s)
- Jari Halonen
- From the Heart Center, Kuopio University Hospital, Kuopio, Finland
- Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
| | - Jussi Kärkkäinen
- From the Heart Center, Kuopio University Hospital, Kuopio, Finland
- Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
| | - Helena Jäntti
- Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
- Centre for Prehospital Emergency Care, Kuopio University Hospital, Kuopio, Finland
| | - Tero Martikainen
- Department of Anesthesiology and Operative Services, Kuopio University Hospital, Kuopio, Finland
| | - Antti Valtola
- From the Heart Center, Kuopio University Hospital, Kuopio, Finland
| | - Sten Ellam
- Department of Anesthesiology and Operative Services, Kuopio University Hospital, Kuopio, Finland
| | - Eemu Väliaho
- From the Heart Center, Kuopio University Hospital, Kuopio, Finland
- Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
| | - Elmeri Santala
- From the Heart Center, Kuopio University Hospital, Kuopio, Finland
- Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
| | - Jenni Räsänen
- From the Heart Center, Kuopio University Hospital, Kuopio, Finland
- Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
| | - Auni Juutilainen
- Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
| | - Visa Mahlamäki
- Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
| | - Sini Vasankari
- Department of Clinical Medicine, University of Turku, Turku, Finland
| | - Tommi Vasankari
- The UKK Institute for Health Promotion Research, Tampere, Finland
- The Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Juha Hartikainen
- From the Heart Center, Kuopio University Hospital, Kuopio, Finland
- Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
| |
Collapse
|
|
9
|
El Gindy DMK, Solayman MH, Khorshid R, Schaalan MF, El Wakeel LM. Effect of Clinical and Genetic Factors on the Development of Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting (CABG) in Egyptian Patients Receiving Beta-Blockers. Cardiovasc Drugs Ther 2024; 38:99-108. [PMID: 36107363 PMCID: PMC10876817 DOI: 10.1007/s10557-022-07380-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/03/2022] [Indexed: 11/03/2022]
Abstract
PURPOSE Prophylactic beta-blockers are recommended to prevent postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). Polymorphisms in the beta-1 adrenergic receptor (ADRB1) and G protein-coupled receptor kinase 5 (GRK5) genes are associated with variable responses to beta-blockers. The aim of this study was to determine the clinical and genetic factors that influence the response to beta-blockers for POAF prophylaxis after CABG. METHODS Patients undergoing isolated CABG and receiving prophylactic beta-blockers (n = 249) were prospectively recruited and followed up for 6 postoperative days. Genotyping of ADRB1 rs1801253, and 3 GRK5 SNPs (rs3740563, rs10787959, and rs17098707) was performed. RESULTS Of the 249 patients, 52 patients (20.8%) experienced POAF. Age, hypertension, vasopressor use, calculated POAF risk score, GRK5 rs2230345 T-allele, and GRK5 rs3740563 A-allele were associated with POAF despite beta-blocker prophylaxis. The multivariate analysis revealed that age [odds ratio (OR) 1.06, 95% CI 1.02-1.11, p = 0.003] and GRK5 rs2230345 T-allele [OR 2.81, 95% CI 1.39-5.67, p = 0.004] were independent predictors of POAF after CABG despite beta-blocker prophylaxis. CONCLUSION GRK5 rs2230345 T-allele carriers were less responsive than AA genotype carriers to prophylactic beta-blockers for the prevention of POAF after CABG. The study was registered on http://clinicaltrials.gov in March 2019, with trial registration number (TRN): NCT03871647.
Collapse
Affiliation(s)
- Dina M K El Gindy
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Misr International University, Cairo, Egypt
| | - Mohamed H Solayman
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
- Clinical Pharmacy Unit, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Ramy Khorshid
- Department of Cardiovascular and Thoracic Surgery, Ain Shams University Hospital, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mona F Schaalan
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Misr International University, Cairo, Egypt
| | - Lamia M El Wakeel
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
| |
Collapse
|
|
10
|
Butova X, Myachina T, Simonova R, Kochurova A, Mukhlynina E, Kopylova G, Shchepkin D, Khokhlova A. The inter-chamber differences in the contractile function between left and right atrial cardiomyocytes in atrial fibrillation in rats. Front Cardiovasc Med 2023; 10:1203093. [PMID: 37608813 PMCID: PMC10440706 DOI: 10.3389/fcvm.2023.1203093] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 07/24/2023] [Indexed: 08/24/2023] Open
Abstract
Introduction The left and right atria (LA, RA) work under different mechanical and metabolic environments that may cause an intrinsic inter-chamber diversity in structure and functional properties between atrial cardiomyocytes (CM) in norm and provoke their different responsiveness to pathological conditions. In this study, we assessed a LA vs. RA difference in CM contractility in paroxysmal atrial fibrillation (AF) and underlying mechanisms. Methods We investigated the contractile function of single isolated CM from LA and RA using a 7-day acetylcholine (ACh)-CaCl2 AF model in rats. We compared auxotonic force, sarcomere length dynamics, cytosolic calcium ([Ca2+]i) transients, intracellular ROS and NO production in LA and RA CM, and analyzed the phosphorylation levels of contractile proteins and actin-myosin interaction using an in vitro motility assay. Results AF resulted in more prominent structural and functional changes in LA myocardium, reducing sarcomere shortening amplitude, and velocity of sarcomere relengthening in mechanically non-loaded LA CM, which was associated with the increased ROS production, decreased NO production, reduced myofibrillar content, and decreased phosphorylation of cardiac myosin binding protein C and troponin I. However, in mechanically loaded CM, AF depressed the auxotonic force amplitude and kinetics in RA CM, while force characteristics were preserved in LA CM. Discussion Thus, inter-atrial differences are increased in paroxysmal AF and affected by the mechanical load that may contribute to the maintenance and progression of AF.
Collapse
Affiliation(s)
- Xenia Butova
- Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russian Federation
| | - Tatiana Myachina
- Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russian Federation
| | - Raisa Simonova
- Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russian Federation
| | - Anastasia Kochurova
- Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russian Federation
| | - Elena Mukhlynina
- Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russian Federation
- Institute of Natural Sciences and Mathematics, Ural Federal University, Yekaterinburg, Russian Federation
| | - Galina Kopylova
- Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russian Federation
| | - Daniil Shchepkin
- Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russian Federation
- Institute of Natural Sciences and Mathematics, Ural Federal University, Yekaterinburg, Russian Federation
| | - Anastasia Khokhlova
- Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russian Federation
- Institute of Physics and Technology, Ural Federal University, Yekaterinburg, Russian Federation
| |
Collapse
|
|
11
|
Trohman RG, Huang HD, Sharma PS. Atrial fibrillation: primary prevention, secondary prevention, and prevention of thromboembolic complications: part 1. Front Cardiovasc Med 2023; 10:1060030. [PMID: 37396596 PMCID: PMC10311453 DOI: 10.3389/fcvm.2023.1060030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Accepted: 03/14/2023] [Indexed: 07/04/2023] Open
Abstract
Atrial fibrillation (AF), is the most common sustained cardiac arrhythmia. It was once thought to be benign as long as the ventricular rate was controlled, however, AF is associated with significant cardiac morbidity and mortality. Increasing life expectancy driven by improved health care and decreased fertility rates has, in most of the world, resulted in the population aged ≥65 years growing more rapidly than the overall population. As the population ages, projections suggest that the burden of AF may increase more than 60% by 2050. Although considerable progress has been made in the treatment and management of AF, primary prevention, secondary prevention, and prevention of thromboembolic complications remain a work in progress. This narrative review was facilitated by a MEDLINE search to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other clinically relevant studies. The search was limited to English-language reports published between 1950 and 2021. Atrial fibrillation was searched via the terms primary prevention, hyperthyroidism, Wolff-Parkinson-White syndrome, catheter ablation, surgical ablation, hybrid ablation, stroke prevention, anticoagulation, left atrial occlusion and atrial excision. Google and Google scholar as well as bibliographies of identified articles were reviewed for additional references. In these two manuscripts, we discuss the current strategies available to prevent AF, then compare noninvasive and invasive treatment strategies to diminish AF recurrence. In addition, we examine the pharmacological, percutaneous device and surgical approaches to prevent stroke as well as other types of thromboembolic events.
Collapse
Affiliation(s)
- Richard G. Trohman
- Section of Electrophysiology, Division of Cardiology, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States
| | | | | |
Collapse
|
|
12
|
Comentale G, Parisi V, Fontana V, Manzo R, Conte M, Nunziata A, Bevilacqua G, Buono M, Hamameh S, Pilato E. The role of Del Nido Cardioplegia in reducing postoperative atrial fibrillation after cardiac surgery in patients with impaired cardiac function. Heart Lung 2023; 60:108-115. [PMID: 36947933 DOI: 10.1016/j.hrtlng.2023.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/27/2023] [Accepted: 03/04/2023] [Indexed: 03/22/2023]
Abstract
BACKGROUND Postoperative atrial fibrillation (POAF) occurs in 20% to 40% of patients who underwent cardiac surgery and can compromise the postoperative course, especially in those with reduced left ventricular ejection fraction. The most common causes are related to surgical trauma and the high variations in volemic and electrolyte balance in the postoperative period. OBJECTIVES As cardioplegic solutions can significantly impact both these factors, the study aimed to assess the role of Del Nido (DN) cardioplegia on the onset of POAF. METHODS A retrospective single-center analysis was carried out on 93 patients undergoing coronary artery bypass graft surgery where cardioplegia was used. The patients were divided into two groups according to the cardioplegic solution (Cold Blood vs Del Nido), and perioperative outcomes were compared. RESULTS POAF occurred in 21.5% of patients; the patients treated with cold blood cardioplegia (CBC) showed a 3-times higher rate of POAF compared to the DN group (OR: 3.44; 95% CI: 1.1 to 10.5; p = 0.029). The CBC group showed higher serum potassium levels both after the cross-clamp removal (p<0.001), at the ICU admission (p = 0.007), and during the first 3 postoperative days (p = 0.009). The defibrillation rate at cross-clamp removal (p = 0.003), the dose of postoperative epinephrine (p<0.001), and the peak of serum troponin (p = 0.01), were lower in the DN Group. CONCLUSION DN cardioplegia showed significantly reduced POAF rates after cardiac surgery by acting on the electrolyte balance, myocardial protection and on the need for postoperative inotropic support.
Collapse
Affiliation(s)
- Giuseppe Comentale
- Dept. of Advanced Biomedical Sciences, University of Napoli "Federico II" - Napoli, Italy.
| | - Valentina Parisi
- Dept. of Translational Medical Sciences - University of Napoli "Federico II", Napoli, Italy
| | - Vittoria Fontana
- Dept. of Advanced Biomedical Sciences, University of Napoli "Federico II" - Napoli, Italy
| | - Rachele Manzo
- Dept. of Advanced Biomedical Sciences, University of Napoli "Federico II" - Napoli, Italy
| | - Maddalena Conte
- Dept. of Translational Medical Sciences - University of Napoli "Federico II", Napoli, Italy
| | - Anna Nunziata
- Dept. of Advanced Biomedical Sciences, University of Napoli "Federico II" - Napoli, Italy
| | - Giovanna Bevilacqua
- Dept. of Advanced Biomedical Sciences, University of Napoli "Federico II" - Napoli, Italy
| | - Mariarita Buono
- Dept. of Advanced Biomedical Sciences, University of Napoli "Federico II" - Napoli, Italy
| | - Shadi Hamameh
- Dept. of Advanced Biomedical Sciences, University of Napoli "Federico II" - Napoli, Italy
| | - Emanuele Pilato
- Dept. of Advanced Biomedical Sciences, University of Napoli "Federico II" - Napoli, Italy
| |
Collapse
|
|
13
|
Serum Catestatin Concentrations Are Increased in Patients with Atrial Fibrillation. J Cardiovasc Dev Dis 2023; 10:jcdd10020085. [PMID: 36826581 PMCID: PMC9965955 DOI: 10.3390/jcdd10020085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 01/25/2023] [Accepted: 02/14/2023] [Indexed: 02/19/2023] Open
Abstract
The autonomic nervous system is crucial in initiating and maintaining atrial fibrillation (AF). Catestatin is a multipurpose peptide that regulates cardiovascular systems and reduces harmful, excessive activity of the sympathetic nervous system by blocking the release of catecholamines. We aimed to determine whether serum catestatin concentrations are associated with AF severity, duration indices, and various clinical and laboratory indicators in these individuals to better define the clinical value of catestatin in patients with AF. The present single center study enrolled 73 participants with AF and 72 healthy age-matched controls. Serum catestatin concentrations were markedly higher in AF patients than controls (14.11 (10.21-26.02) ng/mL vs. 10.93 (5.70-20.01) ng/mL, p = 0.013). Furthermore, patients with a more severe form of AF had significantly higher serum catestatin (17.56 (12.80-40.35) vs. 10.98 (8.38-20.91) ng/mL, p = 0.001). Patients with higher CHA2DS2-VASc scores (17.58 (11.89-37.87) vs. 13.02 (8.47-22.75) ng/mL, p = 0.034) and higher NT-proBNP levels (17.58 (IQR 13.91-34.62) vs. 13.23 (IQR 9.04-22.61), p = 0.036) had significantly higher serum catestatin concentrations. Finally, AF duration correlated negatively with serum catestatin levels (r = -0.348, p = 0.003). The results of the present study implicate the promising role of catestatin in the intricate pathophysiology of AF, which should be explored in future research.
Collapse
|
|
14
|
Zhang Z, Wang W, Zhang Y, You X, Wu J. A potential link between aberrant expression of ECRG4 and atrial fibrillation. Front Oncol 2023; 13:1031128. [PMID: 36910669 PMCID: PMC9992723 DOI: 10.3389/fonc.2023.1031128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 02/08/2023] [Indexed: 02/24/2023] Open
Abstract
Esophageal cancer-related gene-4 (ECRG4), a 148-amino acid propertied and new tumor suppressor, is initially cloned from the normal esophageal epithelium. ECRG4 was found to be expressed not only in esophageal tissues but also in cardiomyocytes. Previous studies demonstrated that ECRG4 is constitutively expressed in esophageal epithelial cells, and its degree of downregulation is directly proportional to prognosis in patients with esophageal cancer. In the heart, ECRG4 shows greater expression in the atria than in the ventricles, which accounts for its heterogeneity. Downregulation of ECRG4 expression level correlates with esophageal cancer, as well as myocardial injuries and arrhythmias. As a result, this review summarizes the possible susceptibility gene, ECRG4 and its associated molecular mechanisms in cancer patients with atrial fibrillation and myocardial injury. The review begins by describing ECRG4's biological background, discusses its expression in the cardiovascular system, lists the clinical and animal research related to the downregulation of ECRG4 in atrial fibrillation, and focuses on its potential role in atrial fibrillation. Downregulation of ECRG4 may increase the risk of atrial fibrillation by affecting ion channels, MMPs expression and inflammatory response. We will then discuss how ECRG4 can be used in the treatment of tumors and arrhythmias, and provide a novel possible strategy to reduce the occurrence of perioperative cardiovascular adverse events in patients with tumors such as esophageal cancer and gastric cancer.
Collapse
Affiliation(s)
- Zuojing Zhang
- Department of Anesthesiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Wei Wang
- Department of Anesthesiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Yuxin Zhang
- Department of Anesthesiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Xingji You
- School of Medicine, Shanghai University, Shanghai, China
| | - Jingxiang Wu
- Department of Anesthesiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| |
Collapse
|
|
15
|
Kamali R, Kwan E, Regouski M, Bunch TJ, Dosdall DJ, Hsu E, Macleod RS, Polejaeva I, Ranjan R. Contribution of atrial myofiber architecture to atrial fibrillation. PLoS One 2023; 18:e0279974. [PMID: 36719871 PMCID: PMC9888724 DOI: 10.1371/journal.pone.0279974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 12/19/2022] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND The role of fiber orientation on a global chamber level in sustaining atrial fibrillation (AF) is unknown. The goal of this study was to correlate the fiber direction derived from Diffusion Tensor Imaging (DTI) with AF inducibility. METHODS Transgenic goats with cardiac-specific overexpression of constitutively active TGF-β1 (n = 14) underwent AF inducibility testing by rapid pacing in the left atrium. We chose a minimum of 10 minutes of sustained AF as a cut-off for AF inducibility. Explanted hearts underwent DTI to determine the fiber direction. Using tractography data, we clustered, visualized, and quantified the fiber helix angles in 8 different regions of the left atrial wall using two reference vectors defined based on anatomical landmarks. RESULTS Sustained AF was induced in 7 out of 14 goats. The mean helix fiber angles in 7 out of 8 selected regions were statistically different (P-Value < 0.05) in the AF inducible group. The average fractional anisotropy (FA) and the mean diffusivity (MD) were similar in the two groups with FA of 0.32±0.08 and MD of 8.54±1.72 mm2/s in the non-inducible group and FA of 0.31±0.05 (P-value = 0.90) and MD of 8.68±1.60 mm2/s (P-value = 0.88) in the inducible group. CONCLUSIONS DTI based fiber direction shows significant variability across subjects with a significant difference between animals that are AF inducible versus animals that are not inducible. Fiber direction might be contributing to the initiation and sustaining of AF, and its role needs to be investigated further.
Collapse
Affiliation(s)
- Roya Kamali
- Department of Bioengineering, University of Utah, Salt Lake City, Utah, United States of America
- Cardiovascular Medicine, University of Utah, Salt Lake City, Utah, United States of America
- Nora Eccles Harrison Cardiovascular Research and Training Institute, Salt Lake City, Utah, United States of America
| | - Eugene Kwan
- Department of Bioengineering, University of Utah, Salt Lake City, Utah, United States of America
- Cardiovascular Medicine, University of Utah, Salt Lake City, Utah, United States of America
- Nora Eccles Harrison Cardiovascular Research and Training Institute, Salt Lake City, Utah, United States of America
| | - Misha Regouski
- Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, United States of America
| | - T. Jared Bunch
- Cardiovascular Medicine, University of Utah, Salt Lake City, Utah, United States of America
| | - Derek J. Dosdall
- Department of Bioengineering, University of Utah, Salt Lake City, Utah, United States of America
- Cardiovascular Medicine, University of Utah, Salt Lake City, Utah, United States of America
- Nora Eccles Harrison Cardiovascular Research and Training Institute, Salt Lake City, Utah, United States of America
- Department of Surgery, University of Utah, Salt Lake City, Utah, United States of America
| | - Ed Hsu
- Department of Bioengineering, University of Utah, Salt Lake City, Utah, United States of America
| | - Rob S. Macleod
- Department of Bioengineering, University of Utah, Salt Lake City, Utah, United States of America
| | - Irina Polejaeva
- Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, United States of America
| | - Ravi Ranjan
- Department of Bioengineering, University of Utah, Salt Lake City, Utah, United States of America
- Cardiovascular Medicine, University of Utah, Salt Lake City, Utah, United States of America
- Nora Eccles Harrison Cardiovascular Research and Training Institute, Salt Lake City, Utah, United States of America
- * E-mail:
| |
Collapse
|
|
16
|
Altieri DI, Etzion Y, Anderson HD. Cannabinoid receptor agonist attenuates angiotensin II-induced enlargement and mitochondrial dysfunction in rat atrial cardiomyocytes. Front Pharmacol 2023; 14:1142583. [PMID: 37113758 PMCID: PMC10126395 DOI: 10.3389/fphar.2023.1142583] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 03/13/2023] [Indexed: 04/29/2023] Open
Abstract
Pathological remodeling of atrial tissue renders the atria more prone to arrhythmia upon arrival of electrical triggers. Activation of the renin-angiotensin system is an important factor that contributes to atrial remodeling, which may result in atrial hypertrophy and prolongation of P-wave duration. In addition, atrial cardiomyocytes are electrically coupled via gap junctions, and electrical remodeling of connexins may result in dysfunction of coordinated wave propagation within the atria. Currently, there is a lack of effective therapeutic strategies that target atrial remodeling. We previously proposed that cannabinoid receptors (CBR) may have cardioprotective qualities. CB13 is a dual cannabinoid receptor agonist that activates AMPK signaling in ventricular cardiomyocytes. We reported that CB13 attenuates tachypacing-induced shortening of atrial refractoriness and inhibition of AMPK signaling in the rat atria. Here, we evaluated the effects of CB13 on neonatal atrial rat cardiomyocytes (NRAM) stimulated by angiotensin II (AngII) in terms of atrial myocyte enlargement and mitochondrial function. CB13 inhibited AngII-induced enhancement of atrial myocyte surface area in an AMPK-dependent manner. CB13 also inhibited mitochondrial membrane potential deterioration in the same context. However, AngII and CB13 did not affect mitochondrial permeability transition pore opening. We further demonstrate that CB13 increased Cx43 compared to AngII-treated neonatal rat atrial myocytes. Overall, our results support the notion that CBR activation promotes atrial AMPK activation, and prevents myocyte enlargement (an indicator that suggests pathological hypertrophy), mitochondrial depolarization and Cx43 destabilization. Therefore, peripheral CBR activation should be further tested as a novel treatment strategy in the context of atrial remodeling.
Collapse
Affiliation(s)
- Danielle I. Altieri
- College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
- Canadian Centre for Agri-Food Research in Health and Medicine (CCARM), Albrechtsen Research Centre, St Boniface Hospital, Winnipeg, MB, Canada
| | - Yoram Etzion
- Cardiac Arrhythmia Research Laboratory, Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva, Israel
- Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Hope D. Anderson
- College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
- Canadian Centre for Agri-Food Research in Health and Medicine (CCARM), Albrechtsen Research Centre, St Boniface Hospital, Winnipeg, MB, Canada
- *Correspondence: Hope D. Anderson,
| |
Collapse
|
|
17
|
Santi ND, Wu KY, Redpath CJ, Nery PB, Huang W, Burwash IG, Bernick J, Wells GA, McArdle B, Chow BWJ, Birnie DH, Garrard L, deKemp RA, Beanlands RSB. Metabolic activity of the left and right atria are differentially altered in patients with atrial fibrillation and LV dysfunction. J Nucl Cardiol 2022; 29:2824-2836. [PMID: 34993894 DOI: 10.1007/s12350-021-02878-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 10/13/2021] [Indexed: 01/22/2023]
Abstract
BACKGROUND Alterations in atrial metabolism may play a role in the perpetuation of atrial fibrillation (AF). This study sought to compare 18F-fluorodeoxyglucose (FDG) uptake on PET, in patients with LV dysfunction versus those without AF. METHODS Seventy-two patients who underwent myocardial viability assessment were evaluated. AF patients (36) had persistent or permanent AF based on history and ECG. Patients without AF (36) were matched to AF patients based on sex, diabetes, age, and LVEF. Maximum and mean FDG Standard Uptake Values (SUV) in the left atrial (LA) wall and right atrial (RA) wall were measured. Tissue-to-blood ratios (TBR) were calculated as atrial wall to blood-pool activity. Atrial volumes were measured by echocardiography. RESULTS Maximum and mean FDG SUV and TBRs were significantly increased in the RA (but not the LA) of patients with AF compared to those without (P < 0.01). When accounting for changes in atrial volume, the presence of AF remained a significant predictor of higher RAMAX, but not RAMEAN FDG uptake. CONCLUSION In patients with LV dysfunction from ischemic cardiomyopathy, LA and RA glucose metabolism are differentially altered in those with persistent atrial fibrillation. Further investigations should elucidate the temporal relationship between AF and glucose metabolic changes, as a potential target for therapy.
Collapse
Affiliation(s)
- Nicolas D Santi
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada.
- Department of Cardiology, University of Toronto Faculty of Medicine, Toronto, ON, Canada.
| | - Kai Yi Wu
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada
- Department of Medicine, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
| | - C J Redpath
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada
| | - Pablo B Nery
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada
| | - Wayne Huang
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada
- Department of Medicine, Queensway Carleton Hospital, Ottawa, ON, Canada
| | - Ian G Burwash
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada
| | - Jordan Bernick
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada
| | - George A Wells
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada
| | - Brian McArdle
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada
- Royal Jubilee Hospital, Victoria, BC, Canada
| | - Benjamin W J Chow
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada
| | - David H Birnie
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada
| | - Linda Garrard
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada
| | - Robert A deKemp
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada
| | - Rob S B Beanlands
- Department of Medicine (Cardiology), University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada.
| |
Collapse
|
|
18
|
Egbe AC, Miranda WR, Anderson JH, DeSimone CV, Andi K, Goda AY, Stephens EH, Dearani JA, Crestanello J, Connolly HM, Deshmukh AJ. Outcome of New-Onset Postoperative Atrial Fibrillation After Cardiac Surgery in Adults With Congenital Heart Disease. JACC Clin Electrophysiol 2022; 8:1407-1416. [PMID: 36424678 PMCID: PMC9991111 DOI: 10.1016/j.jacep.2022.08.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 08/03/2022] [Accepted: 08/05/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND Postoperative atrial fibrillation (POAF) is one of the most common complications after cardiac surgery. POAF is associated with a longer hospital stay, higher healthcare resource utilization, and higher risk of morbidity and mortality. As a result, the American and European guidelines recommend the use of beta-blockers and amiodarone for the prevention of POAF, and in turn, avoid the complications associated with POAF. OBJECTIVES The purpose of this study was to determine the incidence, risk factors, and prognostic implications of new-onset POAF after cardiac surgery in adults with congenital heart disease (CHD). METHODS A retrospective study was conducted among adults with CHD who underwent cardiac surgery (2003-2019). POAF and late-onset atrial fibrillation (AF) were defined as AF occurring within and after 30 days postoperatively, respectively. RESULTS Of 1,598 patients (mean age 39 ± 13 years, 51% men), 335 (21%) developed POAF. Risk factors associated with POAF were older age, hypertension, left atrial (LA) reservoir strain and right atrial (RA) dysfunction, and nonsystemic atrioventricular valve regurgitation. Of 1,291 patients (81%) with follow-up ≥12 months, the annual incidence of late-onset AF was 1.5% and was higher in patients with POAF compared with those without POAF (5.9% vs 0.4%; P < 0.001). Risk factors associated with late-onset AF were POAF, older age, severe CHD, and LA and RA dysfunction. Of the 1,291 patients, 63 (5%) died during follow-up, and the risk factors associated with all-cause mortality were older age, severe CHD, hypertension, left ventricular systolic dysfunction, and LA and RA dysfunction. POAF was not associated with all-cause mortality. CONCLUSIONS POAF was common in adults with CHD and was associated with late-onset AF but not all-cause mortality. Atrial dysfunction was independently associated with POAF, late-onset AF, and all-cause mortality. These risk factors can be used to identify patients at risk for POAF and provide a foundation for prospective studies assessing the efficacy of prophylactic therapies in this population.
Collapse
Affiliation(s)
- Alexander C Egbe
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
| | - William R Miranda
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Jason H Anderson
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Kartik Andi
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Ahmed Y Goda
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Joseph A Dearani
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Juan Crestanello
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Heidi M Connolly
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Abhishek J Deshmukh
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| |
Collapse
|
|
19
|
Yang MU, Lee DI, Park S. Automated diagnosis of atrial fibrillation using ECG component-aware transformer. Comput Biol Med 2022; 150:106115. [PMID: 36179512 DOI: 10.1016/j.compbiomed.2022.106115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 09/03/2022] [Accepted: 09/17/2022] [Indexed: 11/03/2022]
Abstract
Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide and imposes a substantial economic burden on the public healthcare system due to its high morbidity and mortality. Early detection of AF is crucial in providing timely treatment and preventing complications such as stroke and other thromboembolism. For AF diagnosis, the 12-lead electrocardiogram (ECG) has been established as the gold standard. However, it requires the clinical experiences of cardiologists and may be vulnerable to inter-observer variability. Although automated AF diagnostic techniques based on deep neural networks (DNN) have been proposed, most studies were conducted using small-scale datasets, resulting in the over-fitting problem. Furthermore, they have not fully exploited ECG components such as P-wave, QRS-complex, and T-wave contrary to the approach adopted by cardiologists who interpret ECG by considering its components. To overcome these limitations, this study presents the component-aware transformer (CAT), which segments the ECG waveform into each component, vectorizes them with length and types information into one vector, and used it as the input of the transformer. We conducted extensive experiments to evaluate the CAT using a large-scale dataset called Shaoxing Hospital Zhejiang University School of Medicine database (AF: 1,780 cases, non-AF: 8,866 cases). The quantitative evaluations demonstrate that the CAT outperforms the conventional deep learning techniques on both single- and 12-lead ECG signals. Moreover, the CAT trained on single-lead ECG is comparable to that of a 12-lead analysis, while conventional methods degraded significantly in performance. Consequently, the CAT is applicable to various single-channel signals such as airway pressure, photoplethysmogram, and blood pressure.
Collapse
Affiliation(s)
- Min-Uk Yang
- Medical AI Research Team, Chungbuk National University Hospital, Cheongju-si, Chungcheongbuk-do, 28644, Republic of Korea.
| | - Dae-In Lee
- Department of Cardiology, Chungbuk National University Hospital, Cheongju-si, Chungcheongbuk-do, 28644, Republic of Korea.
| | - Seung Park
- Department of Biomedical Engineering, Chungbuk National University Hospital, Cheongju-si, Chungcheongbuk-do, 28644, Republic of Korea.
| |
Collapse
|
|
20
|
Al-Seykal I, Bose A, Chevli PA, Hashmath Z, Sharma N, Mishra AK, Laidlaw D. Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cryoballoon ablation outcomes for paroxysmal atrial fibrillation. World J Cardiol 2022; 14:537-545. [PMID: 36339889 PMCID: PMC9627355 DOI: 10.4330/wjc.v14.i10.537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 06/18/2022] [Accepted: 09/06/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Cryoballoon ablation (CBA) is recommended for patients with paroxysmal atrial fibrillation (AF) refractory to antiarrhythmic drugs. However, only 80% of patients benefit from initial CBA. There is growing evidence that pretreatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) decreases the recurrence of AF postablation, particularly in nonparoxysmal AF undergoing radiofrequency ablation. The role of ACEIs and ARBs in patients with paroxysmal AF in CBA remains unknown. We decided to investigate the role of ACEIs and ARBs in preventing the recurrence of atrial arrhythmia (AA) following CBA for paroxysmal AF. AIM To investigate the role of ACEIs and ARBs in preventing recurrence of AA following CBA for paroxysmal AF. METHODS We followed 103 patients (age 60.6 ± 9.1 years, 29% women) with paroxysmal AF undergoing CBA 1-year post procedure. Recurrence was assessed by documented AA on electrocardiogram or any form of long-term cardiac rhythm monitoring. A multivariable Cox proportional hazard model was used to assess if ACEI or ARB treatment predicted the risk of AA recurrence. RESULTS After a 1-year follow-up, 19 (18.4%) participants developed recurrence of AA. Use of ACEI or ARB therapy was noted in the study population. Patients on ACEI/ARB had a greater prevalence of hypertension and coronary artery disease. On a multivariate model adjusted for baseline demographics and risk factors for AF, ACEI or ARB therapy did not prevent recurrence of AA following CBA (P = 0.72). Similarly, on Kaplan-Meier analysis pretreatment with ACEI/ARB did not predict the time to first recurrence of AA (P = 0.2173). CONCLUSION In our study population, preablation treatment with an ACEI or ARB had no influence on the recurrence of AA following CBA for paroxysmal AF.
Collapse
Affiliation(s)
- Ibragim Al-Seykal
- Department of Medicine, Division of Cardiology, Saint Vincent Hospital, Worcester, MA 01608, United States
| | - Abhishek Bose
- Department of Medicine, Division of Cardiology, University of Massachusetts Chan School of Medicine, Worcester, MA 01608, United States
| | - Parag A Chevli
- Section on Hospital Medicine, Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, United States
| | - Zeba Hashmath
- Department of Medicine, Division of Cardiology, East Carolina University, Greenville, NC 27858, United States
| | - Nitish Sharma
- Department of Medicine, Division of Cardiology, Saint Vincent Hospital, Worcester, MA 01608, United States
| | - Ajay K Mishra
- Department of Medicine, Division of Cardiology, Saint Vincent Hospital, Worcester, MA 01608, United States.
| | - Douglas Laidlaw
- Department of Medicine, Division of Cardiology, Saint Vincent Hospital, Worcester, MA 01608, United States
| |
Collapse
|
|
21
|
Lu YY, Lin FJ, Chen YC, Kao YH, Higa S, Chen SA, Chen YJ. Role of Endothelin-1 in Right Atrial Arrhythmogenesis in Rabbits with Monocrotaline-Induced Pulmonary Arterial Hypertension. Int J Mol Sci 2022; 23:ijms231910993. [PMID: 36232308 PMCID: PMC9569916 DOI: 10.3390/ijms231910993] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/06/2022] [Accepted: 09/15/2022] [Indexed: 12/03/2022] Open
Abstract
Atrial arrhythmias are considered prominent phenomena in pulmonary arterial hypertension (PAH) resulting from atrial electrical and structural remodeling. Endothelin (ET)-1 levels correlate with PAH severity and are associated with atrial remodeling and arrhythmia. In this study, hemodynamic measurement, western blot analysis, and histopathology were performed in the control and monocrotaline (MCT, 60 mg/kg)-induced PAH rabbits. Conventional microelectrodes were used to simultaneously record the electrical activity in the isolated sinoatrial node (SAN) and right atrium (RA) tissue preparations before and after ET-1 (10 nM) or BQ-485 (an ET-A receptor antagonist, 100 nM) perfusion. MCT-treated rabbits showed an increased relative wall thickness in the pulmonary arterioles, mean cell width, cross-sectional area of RV myocytes, and higher right ventricular systolic pressure, which were deemed to have PAH. Compared to the control, the spontaneous beating rate of SAN–RA preparations was faster in the MCT-induced PAH group, which can be slowed down by ET-1. MCT-induced PAH rabbits had a higher incidence of sinoatrial conduction blocks, and ET-1 can induce atrial premature beats or short runs of intra-atrial reentrant tachycardia. BQ 485 administration can mitigate ET-1-induced RA arrhythmogenesis in MCT-induced PAH. The RA specimens from MCT-induced PAH rabbits had a smaller connexin 43 and larger ROCK1 and phosphorylated Akt than the control, and similar PKG and Akt to the control. In conclusion, ET-1 acts as a trigger factor to interact with the arrhythmogenic substrate to initiate and maintain atrial arrhythmias in PAH. ET-1/ET-A receptor/ROCK signaling may be a target for therapeutic interventions to treat PAH-induced atrial arrhythmias.
Collapse
Affiliation(s)
- Yen-Yu Lu
- Division of Cardiology, Sijhih Cathay General Hospital, New Taipei City 22174, Taiwan
- School of Medicine, Fu-Jen Catholic University, New Taipei City 24257, Taiwan
| | - Fong-Jhih Lin
- Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan
| | - Yao-Chang Chen
- Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan
| | - Yu-Hsun Kao
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan
- Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
| | - Satoshi Higa
- Cardiac Electrophysiology and Pacing Laboratory, Division of Cardiovascular Medicine, Makiminato Central Hospital, Okinawa 901-2131, Japan
| | - Shih-Ann Chen
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
- Cardiovascular Center, Taichung Veterans General Hospital, Taichung 40705, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan
- Correspondence: (S.-A.C.); (Y.-J.C.)
| | - Yi-Jen Chen
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan
- Cardiovascular Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
- Correspondence: (S.-A.C.); (Y.-J.C.)
| |
Collapse
|
|
22
|
Changes in cAMP signaling are associated with age-related downregulation of spontaneously beating atrial tissue energetic indices. GeroScience 2022; 45:209-219. [PMID: 35790659 PMCID: PMC9886694 DOI: 10.1007/s11357-022-00609-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 06/15/2022] [Indexed: 02/03/2023] Open
Abstract
The prevalence of atria-related diseases increases exponentially with age and is associated with ATP supply-to-demand imbalances. Because evidence suggests that cAMP regulates ATP supply-to-demand, we explored aged-associated alterations in atrial ATP supply-to-demand balance and its correlation with cAMP levels. Right atrial tissues driven by spontaneous sinoatrial node impulses were isolated from aged (22-26 months) and adult (3-4 months) C57/BL6 mice. ATP demand increased by addition of isoproterenol or 3-Isobutyl-1-methylxanthine (IBMX) and decreased by application of carbachol. Each drug was administrated at the dose that led to a maximal change in beating rate (Xmax) and to 50% of that maximal change in adult tissue (X50). cAMP, NADH, NAD + NADH, and ATP levels were measured in the same tissue. The tight correlation between cAMP levels and the beating rate (i.e., the ATP demand) demonstrated in adult atria was altered in aged atria. cAMP levels were lower in aged compared to adult atrial tissue exposed to X50 of ISO or IBMX, but this difference narrowed at Xmax. Neither ATP nor NADH levels correlated with ATP demand in either adult or aged atria. Baseline NADH levels were lower in aged as compared to adult atria, but were restored by drug perturbations that increased cAMP levels. Reduction in Ca2+-activated adenylyl cyclase-induced decreased cAMP and prolongation of the spontaneous beat interval of adult atrial tissue to their baseline levels in aged tissue, brought energetics indices to baseline levels in aged tissue. Thus, cAMP regulates right atrial ATP supply-to-demand matching and can restore age-associated ATP supply-to-demand imbalance.
Collapse
|
|
23
|
Ramos-Mondragon R, Edokobi N, Hodges SL, Wang S, Bouza AA, Canugovi C, Scheuing C, Juratli L, Abel WR, Noujaim SF, Madamanchi NR, Runge MS, Lopez-Santiago LF, Isom LL. Neonatal Scn1b-null mice have sinoatrial node dysfunction, altered atrial structure, and atrial fibrillation. JCI Insight 2022; 7:152050. [PMID: 35603785 PMCID: PMC9220823 DOI: 10.1172/jci.insight.152050] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 04/12/2022] [Indexed: 11/17/2022] Open
Abstract
Loss-of-function (LOF) variants in SCN1B, encoding the voltage-gated sodium channel β1/β1B subunits, are linked to neurological and cardiovascular diseases. Scn1b-null mice have spontaneous seizures and ventricular arrhythmias and die by approximately 21 days after birth. β1/β1B Subunits play critical roles in regulating the excitability of ventricular cardiomyocytes and maintaining ventricular rhythmicity. However, whether they also regulate atrial excitability is unknown. We used neonatal Scn1b-null mice to model the effects of SCN1B LOF on atrial physiology in pediatric patients. Scn1b deletion resulted in altered expression of genes associated with atrial dysfunction. Scn1b-null hearts had a significant accumulation of atrial collagen, increased susceptibility to pacing induced atrial fibrillation (AF), sinoatrial node (SAN) dysfunction, and increased numbers of cholinergic neurons in ganglia that innervate the SAN. Atropine reduced the incidence of AF in null animals. Action potential duration was prolonged in null atrial myocytes, with increased late sodium current density and reduced L-type calcium current density. Scn1b LOF results in altered atrial structure and AF, demonstrating the critical role played by Scn1b in atrial physiology during early postnatal mouse development. Our results suggest that SCN1B LOF variants may significantly impact the developing pediatric heart.
Collapse
Affiliation(s)
| | | | | | | | | | - Chandrika Canugovi
- Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | | | | | | | - Sami F. Noujaim
- Department of Molecular Pharmacology & Physiology, University of South Florida College of Medicine, Tampa, Florida, USA
| | - Nageswara R. Madamanchi
- Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Marschall S. Runge
- Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | | | - Lori L. Isom
- Department of Pharmacology and
- Department of Neurology and
- Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| |
Collapse
|
|
24
|
Ahmad M, Reddy S, Barkhane Z, Elmadi J, Satish Kumar L, Pugalenthi LS. Hyperthyroidism and the Risk of Cardiac Arrhythmias: A Narrative Review. Cureus 2022; 14:e24378. [PMID: 35619859 PMCID: PMC9126437 DOI: 10.7759/cureus.24378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/21/2022] [Indexed: 11/05/2022] Open
|
|
25
|
Paroxysmal Atrial Fibrillation in Horses: Pathophysiology, Diagnostics and Clinical Aspects. Animals (Basel) 2022; 12:ani12060698. [PMID: 35327097 PMCID: PMC8944606 DOI: 10.3390/ani12060698] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/03/2022] [Accepted: 03/08/2022] [Indexed: 02/07/2023] Open
Abstract
Atrial fibrillation (AF) is the most common arrhythmia in horses causing poor performance. As in humans, the condition can be intermittent in nature, known as paroxysmal atrial fibrillation (pAF). This review covers the literature relating to pAF in horses and includes references to the human literature to compare pathophysiology, clinical presentation, diagnostic tools and treatment. The arrhythmia is diagnosed by auscultation and electrocardiography (ECG), and clinical signs can vary from sudden loss of racing performance to reduced fitness or no signs at all. If left untreated, pAF may promote electrical, functional and structural remodeling of the myocardium, thus creating a substrate that is able to maintain the arrhythmia, which over time may progress into permanent AF. Long-term ECG monitoring is essential for diagnosing the condition and fully understanding the duration and frequency of pAF episodes. The potential to adapt human cardiac monitoring systems and computational ECG analysis is therefore of interest and may benefit future diagnostic tools in equine medicine.
Collapse
|
|
26
|
Aras K, Gams A, Faye R, Brennan J, Goldrick K, Li J, Zhong Y, Chiang CH, Smith EH, Poston MD, Chivers J, Hanna P, Mori S, Ajijola OA, Shivkumar K, Hoover DB, Viventi J, Rogers JA, Bernus O, Efimov IR. Electrophysiology and Arrhythmogenesis in the Human Right Ventricular Outflow Tract. Circ Arrhythm Electrophysiol 2022; 15:e010630. [PMID: 35238622 PMCID: PMC9052172 DOI: 10.1161/circep.121.010630] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 02/17/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Right ventricular outflow tract (RVOT) is a common source of ventricular tachycardia, which often requires ablation. However, the mechanisms underlying the RVOT's unique arrhythmia susceptibility remain poorly understood due to lack of detailed electrophysiological and molecular studies of the human RVOT. METHODS We conducted optical mapping studies in 16 nondiseased donor human RVOT preparations subjected to pharmacologically induced adrenergic and cholinergic stimulation to evaluate susceptibility to arrhythmias and characterize arrhythmia dynamics. RESULTS We found that under control conditions, RVOT has shorter action potential duration at 80% repolarization relative to the right ventricular apical region. Treatment with isoproterenol (100 nM) shortened action potential duration at 80% repolarization and increased incidence of premature ventricular contractions (P=0.003), whereas acetylcholine (100 μM) stimulation alone had no effect on action potential duration at 80% repolarization or premature ventricular contractions. However, acetylcholine treatment after isoproterenol stimulation reduced the incidence of premature ventricular contractions (P=0.034) and partially reversed action potential duration at 80% repolarization shortening (P=0.029). Immunolabeling of RVOT (n=4) confirmed the presence of cholinergic marker VAChT (vesicular acetylcholine transporter) in the region. Rapid pacing revealed RVOT susceptibility to both concordant and discordant alternans. Investigation into transmural arrhythmia dynamics showed that arrhythmia wave fronts and phase singularities (rotors) were relatively more organized in the endocardium than in the epicardium (P=0.006). Moreover, there was a weak but positive spatiotemporal autocorrelation between epicardial and endocardial arrhythmic wave fronts and rotors. Transcriptome analysis (n=10 hearts) suggests a trend that MAPK (mitogen-activated protein kinase) signaling, calcium signaling, and cGMP-PKG (protein kinase G) signaling are among the pathways that may be enriched in the male RVOT, whereas pathways of neurodegeneration may be enriched in the female RVOT. CONCLUSIONS Human RVOT electrophysiology is characterized by shorter action potential duration relative to the right ventricular apical region. Cholinergic right ventricular stimulation attenuates the arrhythmogenic effects of adrenergic stimulation, including increase in frequency of premature ventricular contractions and shortening of wavelength. Right ventricular arrhythmia is characterized by positive spatial-temporal autocorrelation between epicardial-endocardial arrhythmic wave fronts and rotors that are relatively more organized in the endocardium.
Collapse
Affiliation(s)
- Kedar Aras
- Department of Biomedical Engineering, the George Washington University, Washington, DC
- Department of Materials Science and Engineering, Ohio State University, Columbus, OH
| | - Anna Gams
- Department of Biomedical Engineering, the George Washington University, Washington, DC
| | - Rokhaya Faye
- Department of Biomedical Engineering, the George Washington University, Washington, DC
- LIRYC Institute, Bordeaux University, France
| | - Jaclyn Brennan
- Department of Biomedical Engineering, the George Washington University, Washington, DC
| | - Katherine Goldrick
- Department of Biomedical Engineering, the George Washington University, Washington, DC
| | - Jinghua Li
- Department of Biomedical Engineering, Northwestern University, Evanston, IL
- Department of Materials Science and Engineering, Ohio State University, Columbus, OH
| | - Yishan Zhong
- Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, IL
| | - Chia-Han Chiang
- Department of Biomedical Engineering, Duke University, Durham, NC
| | - Elizabeth H. Smith
- Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN
| | - Megan D. Poston
- Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN
| | - Jacqueline Chivers
- Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN
| | - Peter Hanna
- UCLA Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, University of California Los Angeles, Los Angeles, CA
| | - Shumpei Mori
- UCLA Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, University of California Los Angeles, Los Angeles, CA
| | - Olujimi A. Ajijola
- UCLA Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, University of California Los Angeles, Los Angeles, CA
| | - Kalyanam Shivkumar
- UCLA Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, University of California Los Angeles, Los Angeles, CA
| | - Donald B. Hoover
- Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN
| | - Jonathan Viventi
- Department of Biomedical Engineering, Duke University, Durham, NC
| | - John A. Rogers
- Department of Biomedical Engineering, Northwestern University, Evanston, IL
| | | | - Igor R. Efimov
- Department of Biomedical Engineering, the George Washington University, Washington, DC
| |
Collapse
|
|
27
|
Petraglia L, Conte M, Comentale G, Cabaro S, Campana P, Russo C, Amaranto I, Bruzzese D, Formisano P, Pilato E, Ferrara N, Leosco D, Parisi V. Epicardial Adipose Tissue and Postoperative Atrial Fibrillation. Front Cardiovasc Med 2022; 9:810334. [PMID: 35187125 PMCID: PMC8854347 DOI: 10.3389/fcvm.2022.810334] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 01/06/2022] [Indexed: 11/13/2022] Open
Abstract
Background Atrial fibrillation (AF) often occurs after cardiac surgery and is associated with increased risk of stroke and mortality. Prior studies support the important role of inflammation in the pathogenesis of postoperative atrial fibrillation (POAF). It is known that an increased volume and a pro-inflammatory phenotype of epicardial adipose tissue (EAT) are both associated with AF onset in non surgical context. In the present study, we aim to evaluate whether also POAF occurrence may be triggered by an increased production of inflammatory mediators from EAT. Methods The study population was composed of 105 patients, with no history of paroxysmal or permanent AF, undergoing elective cardiac surgery. After clinical evaluation, all patients performed an echocardiographic study including the measurement of EAT thickness. Serum samples and EAT biopsies were collected before surgery. Levels of 10 inflammatory cytokines were measured in serum and EAT conditioned media. After surgery, cardiac rhythm was monitored for 7 days. Results Forty-four patients (41.3%) developed POAF. As regard to cardiovascular therapy, only statin use was significantly lower in POAF patients (65.1% vs. 84.7%; p-0.032). Levels of Monocyte Chemoattractant Protein-1 (MCP-1), in both serum and EAT, were significantly higher in POAF patients (130.1 pg/ml vs. 68.7 pg/ml; p = <0.001; 322.4 pg/ml vs. 153.4 pg/ml; p = 0.028 respectively). EAT levels of IL-6 were significantly increased in POAF patients compared to those in sinus rhythm (SR) (126.3 pg/ml vs. 23 pg/ml; p = <0.005). Conclusion Higher EAT levels of IL-6 and MCP-1 are significantly associated with the occurrence of POAF. Statin therapy seems to play a role in preventing POAF. These results might pave the way for a targeted use of these drugs in the perioperative period.
Collapse
Affiliation(s)
- Laura Petraglia
- Department of Translational Medicine, University of Naples Federico II, Naples, Italy
| | - Maddalena Conte
- Department of Translational Medicine, University of Naples Federico II, Naples, Italy
- Clinica San Michele, Maddaloni, Italy
| | - Giuseppe Comentale
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Serena Cabaro
- Department of Translational Medicine, University of Naples Federico II, Naples, Italy
| | - Pasquale Campana
- Department of Translational Medicine, University of Naples Federico II, Naples, Italy
| | - Carmela Russo
- Department of Translational Medicine, University of Naples Federico II, Naples, Italy
| | - Ilaria Amaranto
- Department of Translational Medicine, University of Naples Federico II, Naples, Italy
| | - Dario Bruzzese
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Pietro Formisano
- Department of Translational Medicine, University of Naples Federico II, Naples, Italy
| | - Emanuele Pilato
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Nicola Ferrara
- Department of Translational Medicine, University of Naples Federico II, Naples, Italy
| | - Dario Leosco
- Department of Translational Medicine, University of Naples Federico II, Naples, Italy
- *Correspondence: Dario Leosco
| | - Valentina Parisi
- Department of Translational Medicine, University of Naples Federico II, Naples, Italy
| |
Collapse
|
|
28
|
Verrier RL, D'Avila A. Atrial Ischemia: an Underappreciated Piece of the Atrial Fibrillation Mosaic. Heart Rhythm 2022; 19:1245-1246. [PMID: 35041925 DOI: 10.1016/j.hrthm.2022.01.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 01/12/2022] [Indexed: 11/24/2022]
Affiliation(s)
- Richard L Verrier
- Beth Israel Deaconess Medical Center, Department of Medicine, Division of Cardiovascular Medicine, Harvard Medical School, Boston MA, USA.
| | - Andre D'Avila
- Beth Israel Deaconess Medical Center, Department of Medicine, Division of Cardiovascular Medicine, Harvard Medical School, Boston MA, USA
| |
Collapse
|
|
29
|
Buffle E, Johner N, Namdar M, Shah D. The significance of pulmonary veins isolation radiofrequency time and the evolution of left atrium volume on a twelve-year observational follow-up of paroxysmal atrial fibrillation patients. Indian Heart J 2022; 74:120-126. [PMID: 35101393 PMCID: PMC9039693 DOI: 10.1016/j.ihj.2022.01.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 10/17/2021] [Accepted: 01/26/2022] [Indexed: 11/25/2022] Open
Abstract
Aims Pulmonary vein isolation (PVI) is the treatment of choice of paroxysmal atrial fibrillation (PAF). However, radiofrequency delivery at extra-PV sites may be additionally required. We compared clinical and procedural characteristics of patients undergoing PVI alone versus adjunctive extra-PV substrate modification, at first procedure and repeat procedures for AF recurrence. Methods 587 patients with PAF undergoing radiofrequency (RF) ablation were retrospectively included. Extra-PV ablation was performed in case of sustained AF despite PVI, or at re-do procedures without PV conduction recovery. Demographic, clinical and electrophysiological predictors of survival without re-intervention were analysed in patients’ groups having undergone one (G1), two (G2) or three or more procedures (G3). Results At baseline procedure, PV RF ablation time was shorter in G1 compared to G2/G3 whereas extra-PV RF ablation time was greater in G3 compared to G1. The proportion of patients requiring PV re-isolation decreased with repeat procedures. Smaller LA before procedure 1 (p1) or p2 was associated with PV reconnection at p2. Conversely larger LA before p1 was associated with extra-PV substrate modification at p2. Late re-do procedure timing (>1yr) was associated with increasing LA volume. Only longer PV and total RF time predicted poorer survival free from AF without re-intervention. Conclusion Longer PV RF time predicted requirement for re-ablation during follow-up. Smaller LA size predicted an increased probability of PV reconnection and decreased extra-PV substrate modification at p2. LA size decreased in patients undergoing early re-intervention, whereas it increased in patients undergoing re-intervention later on suggesting ongoing remodelling or progression.
Collapse
|
|
30
|
Chen C, Chen Q, Cheng K, Zou T, Pang Y, Ling Y, Xu Y, Zhu W. Exosomes and Exosomal Non-coding RNAs Are Novel Promises for the Mechanism-Based Diagnosis and Treatments of Atrial Fibrillation. Front Cardiovasc Med 2021; 8:782451. [PMID: 34926627 PMCID: PMC8671698 DOI: 10.3389/fcvm.2021.782451] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 10/26/2021] [Indexed: 12/15/2022] Open
Abstract
Atrial fibrillation (AF) is the most common arrhythmia worldwide and has a significant impact on human health and substantial costs. Currently, there is a lack of accurate biomarkers for the diagnosis and prognosis of AF. Moreover, the long-term efficacy of the catheter ablation in the AF is unsatisfactory. Therefore, it is necessary to explore new biomarkers and treatment strategies for the mechanism-based AF. Exosomes are nano-sized biovesicles released by nearly all types of cells. Since the AF would be linked to the changes of the atrial cells and their microenvironment, and the AF would strictly influence the exosomal non-coding RNAs (exo-ncRNAs) expression, which makes them as attractive diagnostic and prognostic biomarkers for the AF. Simultaneously, the exo-ncRNAs have been found to play an important role in the mechanisms of the AF and have potential therapeutic prospects. Although the role of the exo-ncRNAs in the AF is being actively investigated, the evidence is still limited. Furthermore, there is a lack of consensus regarding the most appropriate approach for exosome isolation and characterization. In this article, we reviewed the new methodologies available for exosomes biogenesis, isolation, and characterization, and then discussed the mechanism of the AF and various levels and types of exosomes relevant to the AF, with the special emphasis on the exo-ncRNAs in the diagnosis, prognosis, and treatment of the mechanism-based AF.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Wenqing Zhu
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China
| |
Collapse
|
|
31
|
Guo G, Watterson S, Zhang SD, Bjourson A, McGilligan V, Peace A, Rai TS. The role of senescence in the pathogenesis of atrial fibrillation: A target process for health improvement and drug development. Ageing Res Rev 2021; 69:101363. [PMID: 34023420 DOI: 10.1016/j.arr.2021.101363] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 01/24/2021] [Accepted: 05/12/2021] [Indexed: 12/11/2022]
Abstract
Cellular senescence is a state of growth arrest that occurs after cells encounter various stresses. Senescence contributes to tumour suppression, embryonic development, and wound healing. It impacts on the pathology of various diseases by secreting inflammatory chemokines, immune modulators and other bioactive factors. These secretory biosignatures ultimately cause inflammation, tissue fibrosis, immunosenescence and many ageing-related diseases such as atrial fibrillation (AF). Because the molecular mechanisms underpinning AF development remain unclear, current treatments are suboptimal and have serious side effects. In this review, we summarize recent results describing the role of senescence in AF. We propose that senescence factors induce AF and have a causative role. Hence, targeting senescence and its secretory phenotype may attenuate AF.
Collapse
|
|
32
|
Mortazavi SH, Oraii A, Goodarzynejad H, Bina P, Jalali A, Ahmadi Tafti SH, Bagheri J, Sadeghian S. Utility of the CHA 2DS 2-VASc Score in Prediction of Postoperative Atrial Fibrillation After Coronary Artery Bypass Graft Surgery. J Cardiothorac Vasc Anesth 2021; 36:1304-1309. [PMID: 34384685 DOI: 10.1053/j.jvca.2021.07.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 06/28/2021] [Accepted: 07/11/2021] [Indexed: 11/11/2022]
Abstract
OBJECTIVE The authors aimed to investigate the role of CHA2DS2-VASc score and its components in prediction of postoperative atrial fibrillation (POAF) after isolated coronary artery bypass graft (CABG) surgery. DESIGN Retrospective cohort. SETTING Single-center university-affiliated tertiary cardiac center. PARTICIPANTS A total of 2,981 consecutive patients who underwent isolated CABG between 2010 and 2012 were included. INTERVENTIONS All patients underwent isolated CABG and were followed until discharge or in-hospital death. The primary outcome was the development of new-onset POAF during the hospital course. MEASUREMENTS AND MAIN RESULTS During hospitalization, continuous electrocardiogram monitoring was used to detect POAF episodes. New-onset POAF developed in 15.8% of patients following isolated CABG. Patients with POAF had significantly higher CHA2DS2-VASc scores than those without POAF (2.66 ± 1.51 v 2.12 ± 1.36, p < 0.001). After adjustment for potential confounders, CHA2DS2-VASc score was significantly associated with POAF (odds ratio [OR]: 1.295, 95% CI: 1.205-1.391). However, further analyses showed that this effect was restricted to patients with a CHA2DS2-VASc score of ≥2 (OR: 1.813, 95% CI: 1.220-2.694). In multivariate analysis of the CHA2DS2-VASc components, age ≥75 (OR: 3.737, 95% CI: 2.702-5.168), age 65 to 74 (OR: 2.126, 1.701-2.658), hypertension (OR: 1.310, 95% CI: 1.051-1.633), and cerebrovascular accident (OR: 1.807, 95% CI: 1.197-2.726) were independent predictors of POAF. However, the association between POAF and female sex, diabetes mellitus, congestive heart failure, and vascular disease was not statistically significant. CONCLUSIONS CHA2DS2-VASc score is a useful tool for the prediction of POAF after isolated CABG. However, the risk should be interpreted cautiously, since the risk score's promising effect relies on only several of its components.
Collapse
Affiliation(s)
| | - Alireza Oraii
- Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Peyvand Bina
- Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Arash Jalali
- Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Jamshid Bagheri
- Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeed Sadeghian
- Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
33
|
Bonou M, Mavrogeni S, Kapelios CJ, Markousis-Mavrogenis G, Aggeli C, Cholongitas E, Protogerou AD, Barbetseas J. Cardiac Adiposity and Arrhythmias: The Role of Imaging. Diagnostics (Basel) 2021; 11:diagnostics11020362. [PMID: 33672778 PMCID: PMC7924558 DOI: 10.3390/diagnostics11020362] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/07/2021] [Accepted: 02/18/2021] [Indexed: 12/13/2022] Open
Abstract
Increased cardiac fat depots are metabolically active tissues that have a pronounced pro-inflammatory nature. Increasing evidence supports a potential role of cardiac adiposity as a determinant of the substrate of atrial fibrillation and ventricular arrhythmias. The underlying mechanism appears to be multifactorial with local inflammation, fibrosis, adipocyte infiltration, electrical remodeling, autonomic nervous system modulation, oxidative stress and gene expression playing interrelating roles. Current imaging modalities, such as echocardiography, computed tomography and cardiac magnetic resonance, have provided valuable insight into the relationship between cardiac adiposity and arrhythmogenesis, in order to better understand the pathophysiology and improve risk prediction of the patients, over the presence of obesity and traditional risk factors. However, at present, given the insufficient data for the additive value of imaging biomarkers on commonly used risk algorithms, the use of different screening modalities currently is indicated for personalized risk stratification and prognostication in this setting.
Collapse
Affiliation(s)
- Maria Bonou
- Department of Cardiology, Laiko General Hospital, 11527 Athens, Greece; (M.B.); (J.B.)
| | - Sophie Mavrogeni
- Department of Cardiology, Onassis Cardiac Surgery Center, 17674 Athens, Greece; (S.M.); (G.M.-M.)
| | - Chris J. Kapelios
- Department of Cardiology, Laiko General Hospital, 11527 Athens, Greece; (M.B.); (J.B.)
- Correspondence: ; Tel.: +30-213-2061032; Fax: +30-213-2061761
| | | | - Constantina Aggeli
- First Department of Cardiology, Hippokration General Hospital, Medical School of National & Kapodistrian University, 11527 Athens, Greece;
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Medical School of National & Kapodistrian University, 11527 Athens, Greece;
| | - Athanase D. Protogerou
- Cardiovascular Prevention & Research Unit, Clinic and Laboratory of Pathophysiology, National & Kapodistrian University Athens School of Medicine, 11527 Athens, Greece;
| | - John Barbetseas
- Department of Cardiology, Laiko General Hospital, 11527 Athens, Greece; (M.B.); (J.B.)
| |
Collapse
|
|
34
|
Heitmann S, Shpak A, Vandenberg JI, Hill AP. Arrhythmogenic effects of ultra-long and bistable cardiac action potentials. PLoS Comput Biol 2021; 17:e1008683. [PMID: 33591969 PMCID: PMC7909657 DOI: 10.1371/journal.pcbi.1008683] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 02/26/2021] [Accepted: 01/08/2021] [Indexed: 12/04/2022] Open
Abstract
Contemporary accounts of the initiation of cardiac arrhythmias typically rely on after-depolarizations as the trigger for reentrant activity. The after-depolarizations are usually triggered by calcium entry or spontaneous release within the cells of the myocardium or the conduction system. Here we propose an alternative mechanism whereby arrhythmias are triggered autonomously by cardiac cells that fail to repolarize after a normal heartbeat. We investigated the proposal by representing the heart as an excitable medium of FitzHugh-Nagumo cells where a proportion of cells were capable of remaining depolarized indefinitely. As such, those cells exhibit bistable membrane dynamics. We found that heterogeneous media can tolerate a surprisingly large number of bistable cells and still support normal rhythmic activity. Yet there is a critical limit beyond which the medium is persistently arrhythmogenic. Numerical analysis revealed that the critical threshold for arrhythmogenesis depends on both the strength of the coupling between cells and the extent to which the abnormal cells resist repolarization. Moreover, arrhythmogenesis was found to emerge preferentially at tissue boundaries where cells naturally have fewer neighbors to influence their behavior. These findings may explain why atrial fibrillation typically originates from tissue boundaries such as the cuff of the pulmonary vein. Cardiac fibrillation is a medical condition where normal heart function is compromised as electrical activity becomes disordered. How fibrillation arises spontaneously is not fully understood. It is generally thought to be triggered by premature depolarization of the cardiac action potential in one or more cells. Those premature beats, known as after-depolarizations, subsequently initiate a self-sustaining rotor in the otherwise normal heart tissue. In this study, we propose an alternative mechanism whereby arrhythmias are initiated by cardiac cells that fail to repolarize of their own accord but still operate normally when embedded in functional heart tissue. We find that such cells can act as focal ectopic sources under appropriate conditions of inter-cellular coupling. Moreover, those cells are more prone to initiating arrhythmia when they are located on natural tissue boundaries. This may explain why atrial fibrillation typically originates from the site where the pulmonary vein attaches to the wall of the heart.
Collapse
Affiliation(s)
- Stewart Heitmann
- Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia
- * E-mail:
| | - Anton Shpak
- Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia
- Victor Chang Cardiac Research Institute Innovation Centre, Darlinghurst, NSW, Australia
| | - Jamie I. Vandenberg
- Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia
- St Vincent’s Clinical School, UNSW Sydney, Kensington, NSW, Australia
| | - Adam P. Hill
- Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia
- Victor Chang Cardiac Research Institute Innovation Centre, Darlinghurst, NSW, Australia
- St Vincent’s Clinical School, UNSW Sydney, Kensington, NSW, Australia
| |
Collapse
|
|
35
|
Xiao FP, Chen MY, Wang L, He H, Jia ZQ, Kuai L, Zhou HB, Liu M, Hong M. Outcomes of new-onset atrial fibrillation in patients with sepsis: A systematic review and meta-analysis of 225,841 patients. Am J Emerg Med 2021; 42:23-30. [PMID: 33429188 DOI: 10.1016/j.ajem.2020.12.062] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 12/15/2020] [Accepted: 12/20/2020] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND The outcomes of new-onset atrial fibrillation (AF) during sepsis are inconsistent and inconclusive. This meta-analysis aims to provide a comprehensive description of the impact of new-onset AF on the prognosis of sepsis. METHODS Three electronic databases (PubMed, Embase, and the Cochrane Library) were searched for relevant studies. Meta-analysis was performed using odds ratios (OR) and 95% confidence intervals (CI) as effect measures. RESULTS A total of 225,841 patients from 13 individual studies were incorporated to the meta-analysis. The summary results revealed that new-onset AF during sepsis was associated with increased odds of in-hospital mortality (pooled OR: 2.09; 95% CI: 1.53-2.86; p < 001), post-discharge mortality (pooled OR: 2.44; 95% CI: 1.81-3.29; p < .001), and stroke (pooled OR:1.88; 95% CI: 1.13-3.14; p < .05). Results also indicated that the incidence of new-onset AF varied from 1.9% for mild sepsis to 46.0% for septic shock. Furthermore, compared to those without AF, people with new-onset AF had longer ICU and hospital stays, as well as a higher recurrence of AF. CONCLUSIONS New-onset AF is frequently associated with adverse outcomes in patients with sepsis. This is a clinical issue that warrants more attention and should be managed appropriately to prevent poor prognosis.
Collapse
Affiliation(s)
- Fang-Ping Xiao
- Department of Cardiology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ming-Yue Chen
- Department of Geriatrics, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Lei Wang
- Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China
| | - Hao He
- Department of Cardiology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhi-Qiang Jia
- Department of Cardiology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Lin Kuai
- Department of Geriatrics, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hai-Bo Zhou
- Department of Cardiology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Meng Liu
- Department of Cardiology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Mei Hong
- Department of Cardiology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Geriatrics, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
| |
Collapse
|
|
36
|
Varotto L, Bregolin G, Paccanaro M, De Boni A, Bonanno C, Perini F. Network meta-analysis on patent foramen ovale: is a stroke or atrial fibrillation worse? Neurol Sci 2021; 42:101-109. [PMID: 33244742 PMCID: PMC7819966 DOI: 10.1007/s10072-020-04922-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 11/18/2020] [Indexed: 01/15/2023]
Abstract
OBJECTIVE Systematic reviews suggest that patent foramen ovale closure (PFOc) is performed percutaneously with low complication rates. We did a network meta-analysis (NMA) comparing devices for PFO closures, evaluating safety and efficacy of transcatheter PFOc in preventing neurological events in patients with stroke when compared with medical therapy (MT), and assessing risk of atrial fibrillation (AF). METHODS We searched 3 databases (MEDLINE, EMBASE, CENTRAL/CCTR) identifying six randomized controlled trials from 2012 until December 2019. We performed a Bayesian NMA; number-needed-to-treat and number-needed-to-harm were derived by applying the estimated odds ratios (ORs). The likelihood of being helped or harmed (LHH) was evaluated to estimate the risk-effectiveness balance. RESULTS The 3560 patients allocated to PFOc were less subject to a stroke than patients with MT. The overall ORs of PFOc versus MT were 0.41 with fixed-effects, and 0.22 with random-effects model. NMA proves that PFOc induces AF episodes significantly higher than MT, even when analysis is limited to only new episodes of "serious AF." LHH (0.68 fixed-effects, 0.79 random-effects) showed that strokes saved are less than cases of AFs added. By considering only serious AF, strokes saved are higher than serious AFs induced by the PFOc (LHH was 3.46 and 4.00 respectively). CONCLUSIONS NMA supported PFOc in patients with cryptogenic stroke, confirming that devices are better than MT, but increase the risk of AF by over 2/4 times (serious or unserious AF). Considering serious AFs (real risky clinical condition), patients have more advantages in being treated, since LHH is ≥ 3-4.
Collapse
Affiliation(s)
- Leonardo Varotto
- Department of Cardiology, San Bortolo Hospital, viale Rodolfi 37, 36100, Vicenza, Italy.
| | - Gianni Bregolin
- Department of Prevention, AULSS 8 Berica, via IV Novembre 46, 36100, Vicenza, Italy
| | - Mariemma Paccanaro
- Department of Cardiology, San Bortolo Hospital, viale Rodolfi 37, 36100, Vicenza, Italy
| | - Antonella De Boni
- Department of Neurology, San Bortolo Hospital, viale Rodolfi 37, 36100, Vicenza, Italy
| | - Carlo Bonanno
- Department of Cardiology, San Bortolo Hospital, viale Rodolfi 37, 36100, Vicenza, Italy
| | - Francesco Perini
- Department of Neurology, San Bortolo Hospital, viale Rodolfi 37, 36100, Vicenza, Italy
| |
Collapse
|
|
37
|
Kalinin R, Suchkov I, Mzhavanadze N, Povarov V. Hemostatic system in patients with cardiovascular implantable electronic devices. KARDIOLOGIYA I SERDECHNO-SOSUDISTAYA KHIRURGIYA 2021; 14:292. [DOI: 10.17116/kardio202114041292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/10/2024]
|
|
38
|
Crispi V, Isaac E, Abah U, Shackcloth M, Lopez E, Eadington T, Taylor M, Kandadai R, Marshall NR, Gurung A, Rogers LJ, Marchbank A, Qadri S, Loubani M. Surgical factors associated with new-onset postoperative atrial fibrillation after lung resection: the EPAFT multicentre study. Postgrad Med J 2020; 98:177-182. [PMID: 33310899 DOI: 10.1136/postgradmedj-2020-138904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 10/19/2020] [Accepted: 10/29/2020] [Indexed: 11/04/2022]
Abstract
PURPOSE OF THE STUDY Postoperative atrial fibrillation (POAF) is a recognised complication in approximately 10% of major lung resections. In order to best target preoperative treatment, this study aimed at determining the association of incidence of POAF in patients undergoing lung resection to surgical and anatomical factors, such as surgical approach, extent of resection and laterality. STUDY DESIGN Evaluation of Post-operative Atrial Fibrillation in Thoracic surgery (EPAFT): a multicentre, population-based, retrospective, cross-sectional, observational study including 1367 patients undergoing lung resections between April 2016 and March 2017. The primary outcome was the presence of POAF following resection. POAF was defined as at least one episode of symptomatic or asymptomatic AF confirmed by ECG within 7 days from the thoracic procedure or prior to discharge from the hospital. RESULTS POAF was observed in 7.4% of patients: 3.1% in minor resection (video-assisted thoracoscopic surgery (VATS): 2.5%; thoracotomy: 3.8%), 9.0% in simple lobectomy (VATS: 7.3%, thoracotomy: 9.9%), 6.0% in complex resection (thoracotomy: 6.3%) and 11.4% in pneumonectomy. POAF was higher in left (4.0%) vs right (2.4%) minor resections, and in left (9.9%) vs right (8.3%) lobectomy, but higher in right (7.5%) complex resections, and the highest in right pneumonectomy (17.6%). No significant variations were observed as per sex, laterality or resected lobes. A positive univariable and multivariable association was observed for increasing age and increasing extent of resection, but not thoracotomy. Median (Q1-Q3) hospital stay was 9 (7-14) days in POAF and 5 (4-7) days in non-AF patients (p<0.001), with an increased cerebrovascular accident burden (p<0.001) and long-term mortality (p<0.001). CONCLUSIONS Among patients undergoing lung resection, POAF was significantly associated with age, increasing invasiveness of approach and increasing extent of resection. In addition, POAF carried a significant long-term mortality rate and burden of cerebrovascular accident. Appropriate prophylaxis should be targeted at these groups.
Collapse
Affiliation(s)
- Vassili Crispi
- Hull York Medical School, University of Hull, Hull, Kingston upon Hull, UK .,Department of Thoracic Surgery, Castle Hill Hospital, Cottingham, East Riding of Yorkshire, UK
| | - Emmanuel Isaac
- Department of Thoracic Surgery, Castle Hill Hospital, Cottingham, East Riding of Yorkshire, UK
| | - Udo Abah
- Department of Thoracic Surgery, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK
| | - Michael Shackcloth
- Department of Thoracic Surgery, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK
| | - Eileen Lopez
- Department of Thoracic Surgery, Wythenshawe Hospital, Manchester, UK
| | - Thomas Eadington
- Department of Thoracic Surgery, Wythenshawe Hospital, Manchester, UK
| | - Marcus Taylor
- Department of Thoracic Surgery, Wythenshawe Hospital, Manchester, UK
| | - Rammohan Kandadai
- Department of Thoracic Surgery, Wythenshawe Hospital, Manchester, UK
| | - Neil R Marshall
- Peninsula Medical School, University of Plymouth, Plymouth, Devon, UK
| | - Anil Gurung
- Great Western Hospital Foundation NHS Trust, Swindon, Swindon, UK
| | - Luke J Rogers
- Department of Thoracic Surgery, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Adrian Marchbank
- Department of Thoracic Surgery, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Suhail Qadri
- Department of Thoracic Surgery, Castle Hill Hospital, Cottingham, East Riding of Yorkshire, UK
| | - Mahmoud Loubani
- Department of Thoracic Surgery, Castle Hill Hospital, Cottingham, East Riding of Yorkshire, UK
| |
Collapse
|
|
39
|
Brown SM, Larsen NK, Thankam FG, Agrawal DK. Fetal cardiomyocyte phenotype, ketone body metabolism, and mitochondrial dysfunction in the pathology of atrial fibrillation. Mol Cell Biochem 2020; 476:1165-1178. [PMID: 33188453 DOI: 10.1007/s11010-020-03980-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 11/06/2020] [Indexed: 10/23/2022]
Abstract
Atrial fibrillation (AF) is the most common cardiac arrhythmia diagnosed in clinical practice. Even though hypertension, congestive heart failure, pulmonary disease, and coronary artery disease are the potential risk factors for AF, the underlying molecular pathology is largely unknown. The reversion of the mature cardiomyocytes to fetal phenotype, impaired ketone body metabolism, mitochondrial dysfunction, and the cellular effect of reactive oxygen species (ROS) are the major underlying biochemical events associated with the molecular pathology of AF. On this background, the present manuscript sheds light into these biochemical events in regard to the metabolic derangements in cardiomyocyte leading to AF, especially with respect to structural, contractile, and electrophysiological properties. In addition, the article critically reviews the current understanding, potential demerits, and translational strategies in the management of AF.
Collapse
Affiliation(s)
- Sean M Brown
- Creighton University School of Medicine, Omaha, NE, 68178, USA
| | | | - Finosh G Thankam
- Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766, USA
| | - Devendra K Agrawal
- Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766, USA.
| |
Collapse
|
|
40
|
Gupta A, Shields KJ, Manzi S, Wasko MC, Sharma TS. Association of Hydroxychloroquine Use With Decreased Incident Atrial Fibrillation in Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken) 2020; 73:828-832. [PMID: 33098269 DOI: 10.1002/acr.24494] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 10/20/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVE To study the relationship between hydroxychloroquine (HCQ) use and new-onset atrial fibrillation in patients with systemic lupus erythematosus (SLE). METHODS A retrospective cohort of adult patients with SLE was constructed from December 1, 2014 to May 30, 2017. Patients were categorized as either HCQ users or nonusers. The primary outcome was incident atrial fibrillation. Secondary outcomes included incident ventricular arrhythmias (composite of ventricular tachycardia, ventricular fibrillation, or torsades de pointes). Outcomes were adjudicated by review of the electronic health record. Statistical analyses included simple and multivariable logistic regression tests to estimate the association between HCQ use and incident atrial fibrillation after adjusting for relevant confounders. Propensity score matching analysis was completed. RESULTS Our study included 1,647 patients with SLE, of which 917 were HCQ users and 730 were nonusers. A total of 23 atrial fibrillation events occurred, including 3 in HCQ users and 20 in nonusers. Logistic regression analysis showed an odds ratio (OR) of 0.12 (95% confidence interval [95% CI] 0.034-0.39, P = 0.0005) for incident atrial fibrillation and 2.39 (95% CI 0.25-23.0, P = 0.45) for ventricular arrhythmias. Results remained significant in the fully adjusted and propensity score-matched models. CONCLUSION In this exploratory study, HCQ use was associated with an 88% decrease in the risk of incident atrial fibrillation in patients with SLE. Considering the increased cardiovascular risk in SLE, incorporation of HCQ into the regimen may be beneficial for both disease manifestations and reducing the risk of atrial fibrillation. Further studies would be needed to confirm the antifibrillatory benefit of this relatively safe and low-cost medication.
Collapse
Affiliation(s)
| | | | - Susan Manzi
- Allegheny Health Network, Pittsburgh, Pennsylvania
| | | | | |
Collapse
|
|
41
|
Brown SM, Larsen NK, Thankam FG, Agrawal DK. Regulatory role of cardiomyocyte metabolism via AMPK activation in modulating atrial structural, contractile, and electrical properties following atrial fibrillation. Can J Physiol Pharmacol 2020; 99:36-41. [PMID: 33049144 DOI: 10.1139/cjpp-2020-0313] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The number of patients diagnosed with atrial fibrillation (AF) has been rising due to increased incidence, enhanced detection methods, and greater survival rates following diagnosis. Due to this increase, AF is now the most commonly diagnosed arrhythmia in clinical practice. AF is characterized by irregular, high-frequency contractions of atrial myocytes that lead to turbulent blood flow and the potential for thrombus formation, stroke, or heart failure. These high-frequency contractions of the atrial myocytes cause an imbalance between metabolic supply and demand. Although advances have been made in understanding the pathophysiology of AF, the etiology and underlying pathogenic mechanism remain unknown. However, recent evidence suggests that cardiomyocyte metabolism involving 5' AMP-activated protein kinase (AMPK) activation is altered in patients with AF. Here, we critically reviewed the current understanding of AMPK activation in AF and how it could affect structural, contractile, and electrophysiological cellular properties in the pathogenesis of AF.
Collapse
Affiliation(s)
- Sean M Brown
- Creighton University School of Medicine, Omaha, NE 68178, USA
| | | | - Finosh G Thankam
- Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA
| | - Devendra K Agrawal
- Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA
| |
Collapse
|
|
42
|
Protective Effect of Vitis labrusca Leaves Extract on Cardiovascular Dysfunction through HMGB1-TLR4-NFκB Signaling in Spontaneously Hypertensive Rats. Nutrients 2020; 12:nu12103096. [PMID: 33050676 PMCID: PMC7601160 DOI: 10.3390/nu12103096] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 10/03/2020] [Accepted: 10/05/2020] [Indexed: 12/14/2022] Open
Abstract
The Vitis labrusca is a grapevine that has antioxidant, neuroprotective, hepatoprotective, and anticarcinogenic activity. However, the effect of Vitis labrusca leaves on the cardiovascular system is yet to be ascertained. The present study was designed to investigate the effects of Vitis labrusca leaves extract (HP1) on cardiovascular remodeling in spontaneously hypertensive rats. Experiments were performed in rats and were randomly divided into the following groups: Wistar Kyoto rat (WKY), normal control group; spontaneously hypertensive rats (SHR), negative control group; SHR + Losa, positive control group (losartan, 10 mg/kg/daily, AT1 receptor blocker) and SHR + HP1 (100 mg/kg/daily). HP1 was orally administered daily for 4 weeks. The HP1 treatment significantly improved blood pressure, electrocardiographic parameters, and echocardiogram parameters compared to hypertensive rats. Additionally, the left ventricular (LV) remodeling and LV dysfunction were significantly improved in HP1-treated hypertensive rats. Furthermore, an increase in fibrotic area has been observed in hypertensive rats compared with WKY. However, administration of HP1 significantly attenuated cardiac fibrosis in hypertensive rats. Moreover, HP1 suppressed the expression of high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), receptor for advanced glycation end products (RAGE), and extracellular signal-regulated kinases (ERK1/2) induced by hypertensive rats, resulting in improved vascular remodeling. Therefore, these results suggest that HP1 can improve the cardiovascular remodeling in hypertensive rats, and the mechanisms may be related to the suppressive effect of HP1 on HMGB1-TLR4-NFκB signaling in the cardiovascular system. Thus, the protective role of the traditional herbal medicine HP1 may provide new insights into the development of therapeutic drugs on the development of hypertensive cardiovascular dysfunction.
Collapse
|
|
43
|
Wetterslev M, Granholm A, Haase N, Hassager C, Hylander Møller M, Perner A. Treatment strategies for new-onset atrial fibrillation in critically ill patients: Protocol for a systematic review. Acta Anaesthesiol Scand 2020; 64:1343-1349. [PMID: 32673400 DOI: 10.1111/aas.13672] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 07/12/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND New-onset atrial fibrillation is frequent in critically ill patients and associated with poorer outcomes in these patients. Numerous interventions are used for the management of new-onset atrial fibrillation, but it is unknown if these interventions improve patient-important outcomes as compared with placebo or no active intervention in adult critically ill patients. METHODS/DESIGN We will conduct a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials assessing pharmacological and non-pharmacological interventions of new-onset atrial fibrillation as compared with placebo or no active intervention in adult critically ill patients. The primary outcomes are mortality, adverse events and health-related quality of life. We will search the following databases: MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, Science Citation Index and BIOSIS and follow the recommendations by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We will evaluate the overall certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. DISCUSSION New-onset atrial fibrillation is common in adult critically ill patients. However, the balance between the desirable and undesirable effects of pharmacological and non-pharmacological interventions is unknown. The outlined systematic review aims to provide updated data on this topic. REGISTRATION Submitted to PROSPERO (CRD42020187178 ). Status: accepted.
Collapse
Affiliation(s)
- Mik Wetterslev
- Department of Intensive Care Copenhagen University Hospital Rigshospitalet, Copenhagen Denmark
| | - Anders Granholm
- Department of Intensive Care Copenhagen University Hospital Rigshospitalet, Copenhagen Denmark
| | - Nicolai Haase
- Department of Intensive Care Copenhagen University Hospital Rigshospitalet, Copenhagen Denmark
| | - Christian Hassager
- Department of Cardiology Copenhagen University Hospital Rigshospitalet, Copenhagen Denmark
| | - Morten Hylander Møller
- Department of Intensive Care Copenhagen University Hospital Rigshospitalet, Copenhagen Denmark
| | - Anders Perner
- Department of Intensive Care Copenhagen University Hospital Rigshospitalet, Copenhagen Denmark
| |
Collapse
|
|
44
|
Ganglionated Plexi Ablation for the Treatment of Atrial Fibrillation. J Clin Med 2020; 9:jcm9103081. [PMID: 32987820 PMCID: PMC7598705 DOI: 10.3390/jcm9103081] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 09/15/2020] [Accepted: 09/23/2020] [Indexed: 01/11/2023] Open
Abstract
Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with significant morbidity and mortality. The autonomic nervous system (ANS) plays an important role in the initiation and development of AF, causing alterations in atrial structure and electrophysiological defects. The intrinsic ANS of the heart consists of multiple ganglionated plexi (GP), commonly nestled in epicardial fat pads. These GPs contain both parasympathetic and sympathetic afferent and efferent neuronal circuits that control the electrophysiological properties of the myocardium. Pulmonary vein isolation and other cardiac catheter ablation targets including GP ablation can disrupt the fibers connecting GPs or directly damage the GPs, mediating the benefits of the ablation procedure. Ablation of GPs has been evaluated over the past decade as an adjunctive procedure for the treatment of patients suffering from AF. The success rate of GP ablation is strongly associated with specific ablation sites, surgical techniques, localization techniques, method of access and the incorporation of additional interventions. In this review, we present the current data on the clinical utility of GP ablation and its significance in AF elimination and the restoration of normal sinus rhythm in humans.
Collapse
|
|
45
|
Varga RS, Hornyik T, Husti Z, Kohajda Z, Krajsovszky G, Nagy N, Jost N, Virág L, Tálosi L, Mátyus P, Varró A, Baczkó I. Antiarrhythmic and cardiac electrophysiological effects of SZV-270, a novel compound with combined Class I/B and Class III effects, in rabbits and dogs. Can J Physiol Pharmacol 2020; 99:89-101. [PMID: 32970956 DOI: 10.1139/cjpp-2020-0412] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Cardiovascular diseases are the leading causes of mortality. Sudden cardiac death is most commonly caused by ventricular fibrillation (VF). Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a major cause of stroke and heart failure. Pharmacological management of VF and AF remains suboptimal due to limited efficacy of antiarrhythmic drugs and their ventricular proarrhythmic adverse effects. In this study, the antiarrhythmic and cardiac cellular electrophysiological effects of SZV-270, a novel compound, were investigated in rabbit and canine models. SZV-270 significantly reduced the incidence of VF in rabbits subjected to coronary artery occlusion/reperfusion and reduced the incidence of burst-induced AF in a tachypaced conscious canine model of AF. SZV-270 prolonged the frequency-corrected QT interval, lengthened action potential duration and effective refractory period in ventricular and atrial preparations, blocked I Kr in isolated cardiomyocytes (Class III effects), and reduced the maximum rate of depolarization (V max) at cycle lengths smaller than 1000 ms in ventricular preparations (Class I/B effect). Importantly, SZV-270 did not provoke Torsades de Pointes arrhythmia in an anesthetized rabbit proarrhythmia model characterized by impaired repolarization reserve. In conclusion, SZV-270 with its combined Class I/B and III effects can prevent reentry arrhythmias with reduced risk of provoking drug-induced Torsades de Pointes.
Collapse
Affiliation(s)
- Richárd S Varga
- Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary
| | - Tibor Hornyik
- Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary
| | - Zoltán Husti
- Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary
| | - Zsófia Kohajda
- MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary
| | - Gábor Krajsovszky
- Department of Organic Chemistry, Semmelweis University, Budapest, Hungary
| | - Norbert Nagy
- MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary
| | - Norbert Jost
- Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary
| | - László Virág
- Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary
| | - László Tálosi
- Department of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
| | - Péter Mátyus
- Department of Organic Chemistry, Semmelweis University, Budapest, Hungary
| | - András Varró
- Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary.,MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary
| | - István Baczkó
- Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary
| |
Collapse
|
|
46
|
Aibar J, Schulman S. New-Onset Atrial Fibrillation in Sepsis: A Narrative Review. Semin Thromb Hemost 2020; 47:18-25. [PMID: 32968991 DOI: 10.1055/s-0040-1714400] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Atrial fibrillation (AF) is a frequently identified arrhythmia during the course of sepsis. The aim of this narrative review is to assess the characteristics of patients with new-onset AF related to sepsis and the risk of stroke and death, to understand if there is a need for anticoagulation. We searched for studies on AF and sepsis on PubMed, the Cochrane database, and Web of Science, and 17 studies were included. The mean incidence of new-onset AF in patients with sepsis was 20.6% (14.7% in retrospective studies and 31.6% in prospective). Risk factors for new-onset AF included advanced age, white race, male sex, obesity, history of cardiopulmonary disease, heart or respiratory failure, and higher disease severity score. In-hospital mortality was higher in patients with than in those without new-onset AF in 10 studies. In four studies the overall intensive care unit and hospital mortality rates were comparable between patients with and without new-onset AF, while three other studies did not provide mortality data. One study reported on the in-hospital incidence of stroke, which was 2.6 versus 0.69% in patients with or without new-onset AF, respectively. Seven of the studies provided follow-up data after discharge. In three studies, new-onset AF was associated with excess mortality at 28 days, 1 year, and 5 years after discharge of 34, 21, and 3% patients, respectively. In two studies, the mortality rate was comparable in patients with and without new-onset AF. Postdischarge stroke was reported in five studies, whereof two studies had no events after 30 and 90 days, one study showed a nonsignificant increase in stroke, and two studies demonstrated a significant increase in risk of stroke after new-onset AF. The absolute risk increase was 0.6 to 1.6%. Large prospective studies are needed to better understand the need for anticoagulation after new-onset AF in sepsis.
Collapse
Affiliation(s)
- Jesus Aibar
- Internal Medicine Department, Hospital Clínic, IDIBAPS - University of Barcelona, Spain.,Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Sam Schulman
- Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.,Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
| |
Collapse
|
|
47
|
Genetics and Epigenetics of Atrial Fibrillation. Int J Mol Sci 2020; 21:ijms21165717. [PMID: 32784971 PMCID: PMC7460853 DOI: 10.3390/ijms21165717] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 07/22/2020] [Accepted: 07/27/2020] [Indexed: 12/13/2022] Open
Abstract
Atrial fibrillation (AF) is known to be the most common supraventricular arrhythmia affecting up to 1% of the general population. Its prevalence exponentially increases with age and could reach up to 8% in the elderly population. The management of AF is a complex issue that is addressed by extensive ongoing basic and clinical research. AF centers around different types of disturbances, including ion channel dysfunction, Ca2+-handling abnormalities, and structural remodeling. Genome-wide association studies (GWAS) have uncovered over 100 genetic loci associated with AF. Most of these loci point to ion channels, distinct cardiac-enriched transcription factors, as well as to other regulatory genes. Recently, the discovery of post-transcriptional regulatory mechanisms, involving non-coding RNAs (especially microRNAs), DNA methylation, and histone modification, has allowed to decipher how a normal heart develops and which modifications are involved in reshaping the processes leading to arrhythmias. This review aims to provide a current state of the field regarding the identification and functional characterization of AF-related epigenetic regulatory networks
Collapse
|
|
48
|
Baron Toaldo M, Mazzoldi C, Romito G, Poser H, Contiero B, Cipone M, Guglielmini C. Echocardiographic predictors of first onset of atrial fibrillation in dogs with myxomatous mitral valve disease. J Vet Intern Med 2020; 34:1787-1793. [PMID: 32767718 PMCID: PMC7517854 DOI: 10.1111/jvim.15860] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 07/01/2020] [Accepted: 07/01/2020] [Indexed: 12/27/2022] Open
Abstract
Background Atrial fibrillation (AF) occurs in dogs with myxomatous mitral valve disease (MMVD) as a consequence of left atrial (LA) dilatation, and it affects survival and quality of life. Objectives To evaluate the usefulness of echocardiography in predicting the first occurrence of AF in dogs with MMVD. Animals Forty‐four client‐owned dogs with MMVD, 22 dogs that developed AF, and 22 dogs that maintained sinus rhythm. Methods Retrospective observational study. Medical databases were reviewed for dogs that developed AF during the year after diagnosis of MMVD (AF group). The last echocardiographic examination obtained while still in sinus rhythm was used to derive selected variables. For each dog with AF, a control dog matched for body weight, class of heart failure, and LA dimension was selected. Echocardiographic results including LA volumes and LA speckle tracking echocardiography (STE)‐derived variables were measured. Results Among the tested echocardiographic variables, only LA diameter (P = .03) and left ventricular internal diameter in diastole (P = .03) differed significantly between groups, whereas body weight‐indexed variables of cardiac dimension as well as LA volumes and volume‐derived functional variables were not different. Among the STE‐derived variables, peak atrial longitudinal strain (PALS) results differed significantly between the AF group (23.8% ± 8.6%) and the control group (30.5% ± 9.6%; P = .03). A value of PALS ≤28% predicted AF occurrence with sensitivity and specificity of 0.80 and 0.65, respectively. Conclusions and Clinical Importance Absolute cardiac diameters and LA STE (in particular, PALS) are useful echocardiographic predictors for the development of AF in dogs with MMVD.
Collapse
Affiliation(s)
- Marco Baron Toaldo
- Department of Veterinary Medical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Chiara Mazzoldi
- Department of Veterinary Medical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Giovanni Romito
- Department of Veterinary Medical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Helen Poser
- Department of Animal Medicine, Production and Health, University of Padova, Padua, Italy
| | - Barbara Contiero
- Department of Animal Medicine, Production and Health, University of Padova, Padua, Italy
| | - Mario Cipone
- Department of Veterinary Medical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Carlo Guglielmini
- Department of Animal Medicine, Production and Health, University of Padova, Padua, Italy
| |
Collapse
|
|
49
|
Bektik E, Cowan DB, Wang DZ. Long Non-Coding RNAs in Atrial Fibrillation: Pluripotent Stem Cell-Derived Cardiomyocytes as a Model System. Int J Mol Sci 2020; 21:ijms21155424. [PMID: 32751460 PMCID: PMC7432754 DOI: 10.3390/ijms21155424] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 07/27/2020] [Accepted: 07/28/2020] [Indexed: 12/19/2022] Open
Abstract
Atrial fibrillation (AF) is a type of sustained arrhythmia in humans often characterized by devastating alterations to the cardiac conduction system as well as the structure of the atria. AF can lead to decreased cardiac function, heart failure, and other complications. Long non-coding RNAs (lncRNAs) have been shown to play important roles in the cardiovascular system, including AF; however, a large group of lncRNAs is not conserved between mouse and human. Furthermore, AF has complex networks showing variations in mechanisms in different species, making it challenging to utilize conventional animal models to investigate the functional roles and potential therapeutic benefits of lncRNAs for AF. Fortunately, pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) offer a reliable platform to study lncRNA functions in AF because of certain electrophysiological and molecular similarities with native human CMs. In this review, we first summarize the broad aspects of lncRNAs in various heart disease settings, then focus on their potential roles in AF development and pathophysiology. We also discuss current uses of PSCs in AF research and describe how these studies could be developed into novel therapeutics for AF and other cardiovascular diseases.
Collapse
Affiliation(s)
- Emre Bektik
- Department of Cardiology, Boston Children’s Hospital, Harvard Medical School, 300 Longwood, Boston, MA 02115, USA; (E.B.); (D.B.C.)
| | - Douglas B. Cowan
- Department of Cardiology, Boston Children’s Hospital, Harvard Medical School, 300 Longwood, Boston, MA 02115, USA; (E.B.); (D.B.C.)
| | - Da-Zhi Wang
- Department of Cardiology, Boston Children’s Hospital, Harvard Medical School, 300 Longwood, Boston, MA 02115, USA; (E.B.); (D.B.C.)
- Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA
- Correspondence:
| |
Collapse
|
|
50
|
Liu L, Shen L, Liu S, Tu B, Li G, Hu F, Hu Z, Wu L, Fan X, Zheng L, Ding L, Yao Y. Correlations between low thyroid function and incidence of atrial fibrillation in hypertrophic obstructive cardiomyopathy. Chronic Dis Transl Med 2020; 6:35-45. [PMID: 32226933 PMCID: PMC7096325 DOI: 10.1016/j.cdtm.2020.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Indexed: 10/26/2022] Open
Affiliation(s)
- Li‐Min Liu
- Department of Cardiovascular MedicineClinical EP Lab & Arrhythmia CenterFuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100037China
| | - Li‐Shui Shen
- Department of Cardiovascular MedicineClinical EP Lab & Arrhythmia CenterFuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100037China
| | - Shang‐Yu Liu
- Department of Cardiovascular MedicineClinical EP Lab & Arrhythmia CenterFuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100037China
| | - Bin Tu
- Department of Cardiovascular MedicineClinical EP Lab & Arrhythmia CenterFuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100037China
| | - Guo‐Liang Li
- Department of Cardiovascular MedicineFirst Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxi710061China
| | - Feng Hu
- Department of Cardiovascular MedicineClinical EP Lab & Arrhythmia CenterFuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100037China
| | - Zhi‐Cheng Hu
- Department of Cardiovascular MedicineClinical EP Lab & Arrhythmia CenterFuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100037China
| | - Ling‐Min Wu
- Department of Cardiovascular MedicineClinical EP Lab & Arrhythmia CenterFuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100037China
| | - Xiao‐Han Fan
- Department of Cardiovascular MedicineClinical EP Lab & Arrhythmia CenterFuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100037China
| | - Li‐Hui Zheng
- Department of Cardiovascular MedicineClinical EP Lab & Arrhythmia CenterFuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100037China
| | - Li‐Gang Ding
- Department of Cardiovascular MedicineClinical EP Lab & Arrhythmia CenterFuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100037China
| | - Yan Yao
- Department of Cardiovascular MedicineClinical EP Lab & Arrhythmia CenterFuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100037China
| |
Collapse
|