The Three Integrated Phases of Left Atrial Macrophysiology and Their Interactions

Mehrzad, Raman; Rajab, Mohammad; Spodick, David H.

doi:10.3390/ijms150915146

Cited by 34 publications

(30 citation statements)

References 97 publications

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“…; Hoit, ; Mehrzad et al . ). This booster function contributes 20–40% of the end‐diastolic filling, and becomes a critical factor for cardiac output, especially at high heart rates and under pathological conditions involving the atrioventricular valves.…”

Section: Discussionmentioning

confidence: 97%

“…for ventricular filling during ventricular diastole and is referred to as atrial booster function or 'atrial kick' (Rahimtoola et al 1975;Nicod et al 1986;Blume et al 2011;Trafford et al 2013;Hoit, 2014;Mehrzad et al 2014). This booster function contributes 20-40% of the end-diastolic filling, and becomes a critical factor for cardiac output, especially at high heart rates and under pathological conditions involving the atrioventricular valves.…”

Section: Figure 9 K + Channel Agonists Have No Effect On Cat Alternamentioning

confidence: 99%

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Action potential shortening rescues atrial calcium alternans

Kanaporis

Kalik

Blatter

2018

The Journal of Physiology

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Key points Cardiac alternans refers to a beat‐to‐beat alternation in contraction, action potential (AP) morphology and Ca2+ transient (CaT) amplitude, and represents a risk factor for cardiac arrhythmia, including atrial fibrillation. We developed strategies to pharmacologically manipulate the AP waveform with the goal to reduce or eliminate the occurrence of CaT and contraction alternans in atrial tissue. With combined patch‐clamp and intracellular Ca2+ measurements we investigated the effect of specific ion channel inhibitors and activators on alternans. In single rabbit atrial myocytes, suppression of Ca2+‐activated Cl− channels eliminated AP duration alternans, but prolonged the AP and failed to eliminate CaT alternans. In contrast, activation of K+ currents (IKs and IKr) shortened the AP and eliminated both AP duration and CaT alternans. As demonstrated also at the whole heart level, activation of K+ conductances represents a promising strategy to suppress alternans, and thus reducing a risk factor for atrial fibrillation. Abstract At the cellular level alternans is observed as beat‐to‐beat alternations in contraction, action potential (AP) morphology and magnitude of the Ca2+ transient (CaT). Alternans is a well‐established risk factor for cardiac arrhythmia, including atrial fibrillation. This study investigates whether pharmacological manipulation of AP morphology is a viable strategy to reduce the risk of arrhythmogenic CaT alternans. Pacing‐induced AP and CaT alternans were studied in rabbit atrial myocytes using combined Ca2+ imaging and electrophysiological measurements. Increased AP duration (APD) and beat‐to‐beat alternations in AP morphology lowered the pacing frequency threshold and increased the degree of CaT alternans. Inhibition of Ca2+‐activated Cl− channels reduced beat‐to‐beat AP alternations, but prolonged APD and failed to suppress CaT alternans. In contrast, AP shortening induced by activators of two K+ channels (ML277 for Kv7.1 and NS1643 for Kv11.1) abolished both APD and CaT alternans in field‐stimulated and current‐clamped myocytes. K+ channel activators had no effect on the degree of Ca2+ alternans in AP voltage‐clamped cells, confirming that suppression of Ca2+ alternans was caused by the changes in AP morphology. Finally, activation of Kv11.1 channel significantly attenuated or even abolished atrial T‐wave alternans in isolated Langendorff perfused hearts. In summary, AP shortening suppressed or completely eliminated both CaT and APD alternans in single atrial myocytes and atrial T‐wave alternans at the whole heart level. Therefore, we suggest that AP shortening is a potential intervention to avert development of alternans with important ramifications for arrhythmia prevention and therapy.

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Section: Discussionmentioning

confidence: 97%

Section: Figure 9 K + Channel Agonists Have No Effect On Cat Alternamentioning

confidence: 99%

Action potential shortening rescues atrial calcium alternans

Kanaporis

Kalik

Blatter

2018

The Journal of Physiology

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“…In patients with impaired LV relaxation, increased filling pressure not only declines LA passive function but engenders LA stretch and PV dilation, increasing the risk of AF. In response to decreased early filling, LA active function is augmented to maintain LAEF [ 15 ]. That is, a preserved LAEF infers that the atrial myocardium is healthy and can compensate for the decreased early filling, and the AF-related remodeling process may still be in the reversible phase despite LA dilation.…”

Section: Discussionmentioning

confidence: 99%

Left atrial emptying fraction predicts recurrence of atrial fibrillation after radiofrequency catheter ablation

Chou

Lee

et al. 2018

PLoS ONE

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BackgroundCompared with left atrial (LA) dimension, LA emptying fraction (LAEF) has received less emphasis as a predictor of atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). In addition, patients experiencing post-RFCA AF recurrence may respond to previously ineffective antiarrhythmic drugs (AADs). Classifying these patients into a third RFCA outcome category is recommended.ObjectiveTo identify predictors of RFCA outcome classified into three categories, and to build proportional odds logistic regression models for clinical applicability to predict AF recurrence.MethodsData were retrospectively collected from 483 consecutive patients with drug-refractory AF undergoing RFCA (328 men; age 58.4 ± 11.5 years; 383 paroxysmal). Patients were classified into 3 groups based on the last RFCA outcome: group 1, free from AF without AADs; group 2, free from AF with AADs; and group 3, recurrence of AADs-refractory atrial tachyarrhythmia.ResultsAfter a mean follow-up duration of 64.5 ± 43.2 months and mean ablation procedure number of 1.37 ± 0.68, the RFCA outcome showed 76.0%, 9.5% and 14.5% of patients in groups 1, 2, and 3, respectively. In multivariate analysis, LAEF was the most stable and important predictor of AF recurrence, followed by body mass index, stroke, AF duration, mitral regurgitation, and LA linear ablation. For patients undergoing repeat RFCA, LAEF was the only independent predictor (cutoffs: 43% and 35% for groups 1 and 3, respectively).ConclusionLAEF provides optimal prognostic information regarding the risk stratification of AF patients undergoing RFCA.

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“…The atria have important hemodynamic duties. Atrial contraction contributes to ventricular filling, referred to as “atrial kick” or atrial booster function ( Rahimtoola et al, 1975 ; Trafford et al, 2013 ; Hoit, 2014 ; Mehrzad et al, 2014 ). The contribution to ventricular filling covers a wide dynamic range that can span 20%–40% of ventricular filling at the end of ventricular diastole, depending on factors such as heart rate or as a consequence of atrial remodeling in disease.…”

Section: Discussionmentioning

confidence: 99%