Journal of Clinical Medicine Article The Prevalence of Advanced Interatrial Block and Its Relationship to Left Atrial Function in Patients with Transthyretin Cardiac Amyloidosis Thomas Lindow 1,2,3,* and Per Lindqvist 4 1 Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, NSW 2065, Australia 2 Department of Clinical Physiology, Research and Development, Växjö Central Hospital, Region Kronoberg, 351 88 Växjö, Sweden 3 Clinical Physiology, Clinical Sciences, Lund University, 221 00 Lund, Sweden 4 Department of Clinical Physiology, Surgical and Perioperative Sciences, Umeå University, 901 87 Umeå, Sweden; [email protected] * Correspondence: [email protected]; Tel.: +46-730-62-60-07 Abstract: Background: Advanced interatrial block (aIAB), which is associated with incident atrial fibrillation and stroke, occurs in the setting of blocked interatrial conduction. Atrial amyloid depo- sition could be a possible substrate for reduced interatrial conduction, but the prevalence of aIAB in patients with transthyretin cardiac amyloidosis (ATTR-CA) is unknown. We aimed to describe the prevalence of aIAB and its relationship to left atrial function in patients with ATTR-CA in com- parison to patients with HF and left ventricular hypertrophy but no CA. Methods: The presence of aIAB was investigated among 75 patients (49 patients with ATTR-CA and 26 with HF but no CA). A comprehensive echocardiographic investigation was performed in all patients, including left atrial Citation: Lindow, T.; Lindqvist, P. strain and strain rate measurements. Results: Among patients with ATTR-CA, 27% had aIAB and in The Prevalence of Advanced patients with HF but no CA, this figure was 21%, (p = 0.78). The presence of aIAB was associated Interatrial Block and Its Relationship with a low strain rate during atrial contraction (<0.91 s−1) (OR: 5.2 (1.4–19.9)), even after adjusting to Left Atrial Function in Patients for age and LAVi (OR: 4.5 (1.0–19.19)). Conclusions: Advanced interatrial block is common among with Transthyretin Cardiac patients with ATTR-CA, as well as in patients with heart failure and left ventricular hypertrophy but Amyloidosis. J. Clin. Med. 2021, 10, no CA. aIAB is associated with reduced left atrial contractile function. 2764. https://doi.org/10.3390/ jcm10132764 Keywords: interatrial block; left atrial strain; cardiac amyloidosis; transthyretin amyloid Academic Editor: Roberto De Ponti Received: 17 May 2021 Accepted: 22 June 2021 1. Introduction Published: 23 June 2021 During atrial depolarization, the electrical impulses are propagated from the right to the left atrium through several conduction pathways, including inter-nodal tracts between Publisher’s Note: MDPI stays neutral the atria, e.g., Bachmann’s bundle [1]. In the presence of a block in Bachmann’s bundle, with regard to jurisdictional claims in interatrial block (IAB) may occur. This block can occur with varying grades, from partial published maps and institutional affil- IAB resulting in increased P wave duration only, to advanced IAB (aIAB) in which P wave iations. duration is increased (≥120 ms) and a biphasic P wave pattern occurs in inferior leads (II, III, aVF) [2–5]. In case of a complete block in Bachmann’s bundle, depolarization will follow a caudo-cranial route, in which the right atrium is depolarized first (caudal route) followed by a retrograde depolarization of the left atrium (cranial route, Figure1)[ 6], Copyright: © 2021 by the authors. which explains the biphasic P wave pattern in inferior leads. Licensee MDPI, Basel, Switzerland. IAB in combination with supraventricular arrhythmias is known as Bayes’ syn- This article is an open access article drome [7]. aIAB, but not partial IAB, has been shown to be a significant predictor of distributed under the terms and new-onset and recurrent AF [8]. Furthermore, IAB is highly prevalent in patients with conditions of the Creative Commons embolic stroke [7,9,10]. Due to the retrograde and delayed depolarization of the left Attribution (CC BY) license (https:// atrium, poor left atrial electro-mechanical function is plausible, and this may predispose creativecommons.org/licenses/by/ clot formation [9]. 4.0/). J. Clin. Med. 2021, 10, 2764. https://doi.org/10.3390/jcm10132764 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, 2764 2 of 10 J. Clin. Med. 2021, 10, 2764 2 of 11 FigureFigure 1. 1.Description Description of of the the atrial atrial depolarization depolarization route route in in advanced advanced interatrial interatrial block block with with zoomed zoomed images of the P waves in inferior leads (II, aVF and III), in the case of a block in Bachmann’s bundle images of the P waves in inferior leads (II, aVF and III), in the case of a block in Bachmann’s bundle (1). Normally, depolarization of the atria travels through the right and left atria through internodal (1). Normally, depolarization of the atria travels through the right and left atria through internodal tracts, e.g., Bachmann’s bundle. Since impulse propagation from the right atrium to the left atrium tracts,is blocked, e.g., Bachmann’s the right atrium bundle. will Since be depolarized impulse propagation first (2) followed from the by right a retrograde atrium to depolarization the left atrium of isthe blocked, left atrium the right (3), resulting atrium will in biphasic be depolarized P waves first in inferior (2) followed leads. byModified a retrograde from [10], depolarization reprinted with of thepermission. left atrium (3), resulting in biphasic P waves in inferior leads. Modified from [10], reprinted with permission. Transthyretin cardiac amyloidosis (ATTR-CA) has received increased attention in re- centTransthyretin years, and prevalence cardiac amyloidosis of the disease (ATTR-CA) has been reported has received to be increased markedly attention higher than in recentpreviously years, expected and prevalence [11]. For of example, the disease approx has beenimately reported one in to eight be markedly patients higher undergoing than previouslytranscatheter expected aortic valvular [11]. For replacement example, approximately [12] and about one one in in eight five patients with undergoing left ven- transcathetertricular hypertrophy aortic valvular and heart replacement failure (HF) [12] could and about be diagnosed one in five with patients ATTR-CA with left[13]. ventricularATTR-CA hypertrophyis nowadays an and important heart failure clinical (HF) reality could for be both diagnosed cardiologists with ATTR-CA[11] and radiol- [13]. ATTR-CAogists [14]. is nowadaysIn ATTR-CA, an importantdeposition clinical of transthyretin reality for (TTR) both cardiologists amyloid fibrils [11 ]occurs and radiol- in the ogistsextracellular [14]. In space ATTR-CA, of the deposition heart, affecting of transthyretin not only the (TTR) ventricles amyloid but fibrils the atria, occurs as inwell the as extracellularresulting in impaired space of theventricular heart, affecting and atrial not function only the [15–17]. ventricles In addition but the atria,to HF, as ATTR-CA well as resulting in impaired ventricular and atrial function [15–17]. In addition to HF, ATTR-CA is is associated with increased risk of arrhythmias, in the form of both conduction abnormal- associated with increased risk of arrhythmias, in the form of both conduction abnormalities, ities, such as bundle branch block or AV block, and atrial fibrillation [18–20]. It is plausible such as bundle branch block or AV block, and atrial fibrillation [18–20]. It is plausible that that conduction within the atrium, as well as between the atria, is affected by ATTR-CA, conduction within the atrium, as well as between the atria, is affected by ATTR-CA, and and that the prevalence of aIAB may therefore be increased in this population. Since both that the prevalence of aIAB may therefore be increased in this population. Since both stroke stroke and atrial fibrillation are common among patients with ATTR-CA [21,22], it is im- and atrial fibrillation are common among patients with ATTR-CA [21,22], it is important to portant to identify reliable predictors of such adverse events. identify reliable predictors of such adverse events. Our primary aim was to describe the prevalence of aIAB in patients with ATTR-CA Our primary aim was to describe the prevalence of aIAB in patients with ATTR-CA in in comparison to patients with HF and left ventricular hypertrophy but no CA. A second- comparison to patients with HF and left ventricular hypertrophy but no CA. A secondary ary aim was to evaluate the association between aIAB and left atrial function. aim was to evaluate the association between aIAB and left atrial function. 2.2. Material Material and and Methods Methods WeWe performed performed an an observational observational study study including including patients patients with with increased increased left ventricularleft ventric- wallular thickness wall thickness and HF, and previously HF, previously included included in a separate in a separate study study on ATTR-CA on ATTR-CA [13]. In [13]. that In study,that study, out of out 2238 of patients 2238 patients with HF, with cardiomyopathy HF, cardiomyopathy or hypertensive or hypertensive heart disease heart disease based onbased hospital on hospital records records (International (International Classification Classification of Diseases of Diseases 10 (ICD-10): 10 (ICD-10): I50, I50, I42, I42, I43 I43 oror I11), I11), 174174 patients had had interventricular interventricular sept septalal thickness thickness (IVSd) (IVSd) exceeding