Targeted Atrial Fibrillation Therapy and Risk Stratification Using Atrial Alternans
Abstract
:1. Introduction
2. Investigating Mechanisms of Atrial Alternans
3. Preclinical Models of Atrial Alternans
4. Atrial Alternans and Risk of Atrial Fibrillation
5. Current Therapeutic Targets and Research Gaps
6. Future Scope: Can Atrial Alternans Guide Atrial Fibrillation Therapy and Risk Stratification?
Authors | Year | Objectives | Model | Primary Results |
---|---|---|---|---|
IN-SILICO AND IN-VITRO STUDIES | ||||
Zhao et al. [24] | 2020 | Investigate the effects of HF-induced electrophysiological and structural remodeling on atrial alternans | Canine atrial 1D model | HF-induced atrial electrical remodeling increased Ca2+ transient amplitude and SR Ca2+ concentration, resulting in increased susceptibility to alternans |
Kanaporis et al. [30] | 2019 | Can K+ agonists prevent the development of Ca2+ transient alternans | Rabbit atrial myocytes | K+ channel agonists can suppress the development of atrial alternans |
Kanaporis et al. [50] | 2016 | Investigate mechanisms of atrial alternans | Rabbit atrial myocytes | Calcium-activated chloride current determines action potential morphology during calcium alternans |
Chang et al. [20] | 2014 | Determine how cellular remodeling in atrial fibrillation patients affects alternans | Human atrial tissue model | Disturbed Ca2+ homeostasis drives proarrhythmic APD alternans in AF patients and may be significantly influenced by RyR kinetics |
Tsai et al. [51] | 2011 | Investigate the effect of mechanical stretch on APD and calcium transient alternans | Atrial myocytes monolayer | The threshold of the APD alternans and calcium transient alternans is significantly reduced |
Kockskämper et al. [52] | 2002 | Study the subcellular properties of Ca2+ alternans in atrial myocytes | Feline atrial myocytes | Focal inhibition of glycolysis mechanisms within a myocyte led to a rise in alternating Ca2+ waves |
Hüser et al. [53] | 2000 | Understand the mechanisms of alternans by evaluating the SR Ca2+ triggers by restricting different glycolysis routes | Feline atrial myocytes | Cardiac alternans result from alterations in the gain of excitation contraction coupling, which is locally controlled around the SR Ca2+ release sites by mechanisms utilizing ATP, produced by glycolytic enzymes |
PRECLINICAL STUDIES | ||||
Liu et al. [23] | 2020 | Can AF-induced remodeling increase the susceptibility to Ca2+ transients and APD alternans | Canine tachypacing model | AF remodeling enhanced spontaneous Ca2+ release, prolonged the refractory period of the Ca2+ transient, increased the slope of the Ca2+ transient restitution curve, and predisposed the hearts to Ca2+ alternans |
Pearman et al. [27] | 2018 | Can age-associated differences in Ca2+ handling predispose animals to a lower threshold atrial alternans | In vivo ovine model | Decreased Ca2+ transient amplitude and slowed reuptake of Ca2+ into the SR driven by increased Ca2+ buffering predisposed the aged myocytes to develop atrial alternans |
Monigatti-Tenkorang et al. [26] | 2014 | Investigate the mechanisms by which intermittent atrial tachycardia promotes sustained AF | In vivo ovine model | Atrial tachycardia causes a pro-fibrillatory substrate and increased atrial repolarization alternans, leading to AF |
Gan et al. [28] | 2013 | Investigate whether the L-type Ca2+ current alters with age, predisposing the heart to AF | Canine model | Aged cells had longer APD and lower peak L-type Ca2+ current densities, leading to slow and discontinuous conduction of the left atria |
David et al. [32] | 1981 | Demonstrate mechanical atrial alternans during programmed atrioventricular pacing with and without A-V block | In vivo canine model | Atrial alternans was demonstrated during rapid atrial stimulation at cycle lengths ranging from 250 to 120 ms |
CLINICAL STUDIES | ||||
Kulkarni et al. [12] | 2021 | Investigate if p-wave alternans is a marker for utility of low-level tragus stimulation in paroxysmal AF patients | Paroxysmal AF patients | Chronic tragus stimulation significantly reduced p-wave alternans in AF patients and atrial alternans helped identify patients likely to benefit from the treatment |
Yoshikawa et al. [36] | 2020 | Pulsus alternans during atrial flutter | Case study | Presence of pulsus alternans, an alternation in the pulse strength, was observed to be instigated by atrial flutter, which ceased on cardioversion |
Siniorakis et al. [13] | 2017 | P-wave alternans and atrial flutter | Case study | Repeated episodes of atrial flutter were observed, always preceded by p-wave alternans |
Lalani et al. [18] | 2013 | Investigate utility of spectral analysis of alternans as a clinical index of propensity to AF | AF patients | Spectral alternans analysis can identify patients with predisposition to AF |
Narayan et al. [19] | 2011 | Investigate if atrial APD alternans reveals vulnerability to AF | AF patients | APD alternans preceded every AF initiation episode and revealed susceptibility to AF |
Hiromoto et al. [37] | 2005 | Investigate the role of atrial alternans in AF | Patients with structural heart disease | Rapid atrial pacing induced discordant alternans, which was associated with initiation of AF |
Kim et al. [31] | 2002 | Study APD restitution kinetics in AF patients | AF patients | AF was related to steeply sloped (>1) APD restitution kinetics and heterogeneity of APD of the atrium played an important role in the persistence of AF |
Narayan et al. [14] | 2002 | Test the hypothesis that atrial flutter can progress to AF via atrial action potential alternans | Atrial flutter patients | Atrial flutter originating at the isthmus initially instigates APD alternans and conduction block, and then progresses to AF |
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviation
AF | Atrial fibrillation |
HF | Heart failure |
APD | Action potential duration |
RyR | Ryanodine receptor |
SR | Sarcoplasmic reticulum |
Vm | Membrane potential |
Ca2+ | Calcium |
K+ | Potassium |
PFA | Pulsed field ablation |
References
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Muthavarapu, N.; Mohan, A.; Manga, S.; Sharma, P.; Bhanushali, A.K.; Yadav, A.; Damani, D.N.; Jais, P.; Walton, R.D.; Arunachalam, S.P.; et al. Targeted Atrial Fibrillation Therapy and Risk Stratification Using Atrial Alternans. J. Cardiovasc. Dev. Dis. 2023, 10, 36. https://doi.org/10.3390/jcdd10020036
Muthavarapu N, Mohan A, Manga S, Sharma P, Bhanushali AK, Yadav A, Damani DN, Jais P, Walton RD, Arunachalam SP, et al. Targeted Atrial Fibrillation Therapy and Risk Stratification Using Atrial Alternans. Journal of Cardiovascular Development and Disease. 2023; 10(2):36. https://doi.org/10.3390/jcdd10020036
Chicago/Turabian StyleMuthavarapu, Neha, Anmol Mohan, Sharanya Manga, Palak Sharma, Aditi Kishor Bhanushali, Ashima Yadav, Devanshi Narendra Damani, Pierre Jais, Richard D. Walton, Shivaram P. Arunachalam, and et al. 2023. "Targeted Atrial Fibrillation Therapy and Risk Stratification Using Atrial Alternans" Journal of Cardiovascular Development and Disease 10, no. 2: 36. https://doi.org/10.3390/jcdd10020036
APA StyleMuthavarapu, N., Mohan, A., Manga, S., Sharma, P., Bhanushali, A. K., Yadav, A., Damani, D. N., Jais, P., Walton, R. D., Arunachalam, S. P., & Kulkarni, K. (2023). Targeted Atrial Fibrillation Therapy and Risk Stratification Using Atrial Alternans. Journal of Cardiovascular Development and Disease, 10(2), 36. https://doi.org/10.3390/jcdd10020036