Atrial Failure as a Clinical Entity

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

VOL. 75, NO. 2, 2020

ª 2020 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

JACC REVIEW TOPIC OF THE WEEK

Atrial Failure as a Clinical Entity JACC Review Topic of the Week Felipe Bisbal, MD, PHD,a,b,c Adrian Baranchuk, MD,d Eugene Braunwald, MD,e Antoni Bayés de Luna, MD, PHD,c,f Antoni Bayés-Genís, MD, PHDa,b,c

ABSTRACT Atrial dysfunction has been widely considered a marker or consequence of other cardiac conditions rather than the cause itself. Here, we propose the term atrial failure as a clinically relevant entity, defined as any atrial dysfunction causing impaired heart performance, symptoms, and worsening quality of life or life expectancy. Aspects of the etiology, mechanisms, and consequences of atrial failure are discussed. Recent advances in cardiac electrophysiology and imaging have improved our understanding of the highly complex atrial anatomy and function, underlying the paramount importance of the atria in optimal heart performance. It is time to reappraise the concept of the failing atrium as a primary cause or aggravating factor of the symptoms in many of our patients. The concept of atrial failure may foster basic and translational research to gain a better understanding of how to identify and manage atrial dysfunction. (J Am Coll Cardiol 2020;75:222–32) © 2020 by the American College of Cardiology Foundation.

“. . . and, if at this time, with its auricle alone

atrial fibrillation (AF) and the increasing sophisticat-

beating, you cut off the apex of the heart with a

ion of cardiac imaging modalities. A deeper under-

pair of scissors, you will see the blood flow out

standing

from the wound with each beat of the auricle.

revealed its crucial role in the hemodynamics of

You will thus realize that the blood gets into the

the heart, but this knowledge is not always trans-

ventricles not through any pull exerted by the distended heart, but through the driving force exerted by the beat of the auricles.”

D

—William Harvey, 1628

of

atrial

structure

and

function

has

lated into clinical practice. A myriad of conditions may impair LA performance by affecting its mechanical and homeostatic functions or its electrical coupling to the ventricle. Impaired left ventricular (LV) hemodynamics, increased thrombo-

espite the observations described by Har-

genicity, and pulmonary hypertension may occur,

vey early in the 17th century and the

leading to highly variable clinical manifestations

foundational physiological properties of

including heart failure (HF), myocardial ischemia,

the left atrium (LA) reported >50 years ago (1,2),

and thromboembolic events (Central Illustration).

the LA has been quite neglected by researchers,

Atrial dysfunction has been widely considered to

and its role in cardiac function minimized. More

be a marker or consequence of other cardiac condi-

recently, the LA has garnered great attention with

tions, rather than a potential cause. In this review, we

the development of interventional therapies for

propose the term atrial failure as an independent,

Listen to this manuscript’s audio summary by

From the aHeart Institute (iCor), University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; bCIBERCV, Instituto de

Editor-in-Chief

Salud Carlos III, Madrid, Spain; cDepartment of Medicine, Universitat Autònoma Barcelona, Barcelona, Spain; dDepartment of

Dr. Valentin Fuster on

Medicine, Division of Cardiology, Heart Rhythm Service, Queen’s University, Kingston General Hospital, Kingston, Ontario,

JACC.org.

Canada; eCardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; and the fInstitut Català Ciències Cardiovasculars, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. This work was supported by Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain (PI18/01227), CIBER Cardiovascular (CB16/11/00403); and La MARATO - TV3 (ID 201527). The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received August 12, 2019; revised manuscript received October 9, 2019, accepted November 5, 2019.

ISSN 0735-1097/$36.00

https://doi.org/10.1016/j.jacc.2019.11.013

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HIGHLIGHTS
Atrial dysfunction is often neglected.
We propose atrial failure as a clinically relevant entity.
The concept of atrial failure may foster research leading to a better understanding of atrial dysfunction.

flow patterns, favoring early diastolic LV

ABBREVIATIONS

filling while avoiding blood stasis (5).

AND ACRONYMS

The left atrial appendage (LAA), a trabeculated, independently attached structure with high anatomical variability, has an important endocrine function. Its separation from the LA body makes appendage blood turnover

highly

dependent

on

systolic

contraction. Loss of LAA contraction (i.e., AF) and specific morphological features have with

blood

stasis

and

AV = atrioventricular HF = heart failure HFpEF = heart failure with preserved ejection fraction

LA = left atrium LAA = left atrial appendage LV = left ventricle

been

diversity of etiologies, mechanisms, and manifesta-

thrombus formation (6). Both atria are con-

MI = myocardial infarction

tions. Aspects of the etiology, mechanisms, and con-

nected by organized bundles of myocytes

PV = pulmonary vein

sequences of atrial failure are discussed.

located at the epicardial anterior interatrial groove (Bachmann’s bundle), septum, and coronary sinus,

DEFINITION OF ATRIAL FAILURE

allowing bi-atrial synchronous activation.

We propose a definition of atrial failure as “any atrial (anatomical,

associated

AF = atrial fibrillation

clinically relevant entity beyond AF and HF, with a

dysfunction

mechanical,

electrical,

and/or rheological, including blood homeostasis) causing impaired heart performance and symptoms, and worsening quality of life or life expectancy, in the absence of significant valvular or ventricular abnormalities.” Other relevant definitions are provided in Table 1. Several aspects of atrial failure have been previously addressed (3); however, as happened with HF syndrome, atrial failure syndrome is likely to be subject to a more refined redefinition in the future as more knowledge on this entity is obtained. Congestive HF may not occur exclusively because of a failing LV. Even with preserved LV function, other conditions (such as a diseased/dysfunctional LA) may impair global heart performance. In the absence of LV disease, atrial fibrotic changes and dysfunction may trigger HF syndrome, stroke, or arrhythmias (Figure 1).

The LA has a crucial role in LV filling and global heart performance and a dynamic interaction with ventricular diastole and systole. Timely atrioventricular (AV) coupling is essential to the synchronization of atrial cycle phases to LV diastole. Inflow to the LA from the PVs occurs during LV systole and isovolumetric relaxation (reservoir function), and accounts for approximately 40% to 50% of the

LV

stroke

volume.

Passive

blood

transfer

during LV diastole (conduit function) constitutes approximately 20% to 30% of stroke volume and precedes the active atrial contraction (booster-pump function), which transfers the remaining volume (w20%–30%) to the LV; retrograde flow to the PVs also occurs (2). The performance of both the reservoir and conduit phases is determined by atrial compliance, ventricular relaxation, and transmitral pressure gradient (7). Conditions impairing any atrial function, especially mechanical

ANATOMY AND FUNCTION OF THE LA

alterations

leading

to

an

abnormal

pressure-volume relationship (8), may affect global cardiac performance, leading to symptoms and

It is thought that partitioning of the heart into inflow

worsening outcomes. In contrast to atrial cardiomy-

and

cepha-

opathy (disease-specific anatomic/histological fea-

lochordates approximately 600 million years ago and

tures associated with myocardial disease), atrial

that an ancestral atrial chamber first developed

failure refers to the functional consequences of any

approximately 100 million years later, in ancient

atrial condition, including but not restricted to pri-

hagfish and lamprey (4). The atrium then became the

mary atrial disease.

outflow

segments

223

Atrial Failure

was

present

in

main inflow component of the heart in vertebrate organisms.

ETIOLOGY OF ATRIAL FAILURE

The LA is a highly complex structure, with close interaction between its anatomical, ultrastructural,

A list of the proposed causes and triggers of atrial

and functional aspects. The LA has 2 parts: the

failure is provided in Table 2.

postero-superior inflow (venous) and antero-inferior

ATRIAL RHYTHM DISORDERS. Synchronous atrial

outflow (vestibular) components. The 3-dimensional

activation allows effective active contraction with

asymmetrical configuration of the systemic pulmo-

timely coupling. Rapid atrial arrhythmias (e.g., AF)

nary vein (PV) attachment allows specific vortical

produce

ineffective

active

contraction.

Rapid,

224

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Atrial Failure

C E NT R AL IL L U STR AT IO N Atrial Failure

Bisbal, F. et al. J Am Coll Cardiol. 2020;75(2):222–32.

Schematic on the causes, mechanisms, and clinical manifestations of atrial failure. The 4D atrial flow image has been reproduced with permission from Garcia et al. (66). AF ¼ atrial fibrillation; AV ¼ atrioventricular; LV ¼ left ventricular.

irregular conduction to the ventricles impairs both

(left bundle branch block or advanced interatrial

systolic and diastolic LV function, associated with

block, respectively). In advanced interatrial block,

tachycardia-induced

short,

derangement in the interatrial contraction sequence

Suboptimal electrical AV coupling, as observed

of atrial failure, HF, and activated thrombogenic

cardiomyopathy

and

irregular LV filling, respectively.

(i.e., interatrial dyssynchrony) is an additional trigger

with a long PR interval and asynchronous right ventricular

pacing,

may

lead

to

inefficient

cascade (9) (Figure 2).

atrial

contraction and reduced ventricular end diastolic

ATRIAL CARDIOMYOPATHY. Fibrosis is a common

filling. This may also be evident when AV coupling is

finding of most primary and secondary atrial pathol-

compromised due to delayed LV or LA activation

ogies, leading to increased stiffness and reduced

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Atrial Failure

T A B L E 1 Definitions

Term

Definition

Example

High fibrosis burden and sphericity causing stroke in a patient with lone atrial fibrillation (CHA2DS2VASc ¼ 0) Advanced atrial dyssynchrony causing abnormal left ventricular filling and symptoms (Figure 3)

Atrial failure

Any atrial dysfunction causing impaired heart performance and symptoms and worsening quality of life or life expectancy, in the absence of significant valvular or ventricular abnormalities

Atrial cardiomyopathy

Diseases of the myocardium associated with mechanical and/or electrical Isolated fibrotic atrial cardiomyopathy leading to dysfunction that usually (but not invariably) exhibit inappropriate atrial impaired atrial function and heart failure fibrosis, hypertrophy, or dilatation and are due to a variety of causes symptoms (Figure 2) (adapted from Maron et al. [64])

Atrial remodeling

Response of atrial myocytes to electrical, mechanical, or metabolic stressors (mainly rapid atrial tachyarrhythmias or pressure and volume overload) leading to persistent change in LA size, function or electrophysiological properties (adapted from Thomas and Abhayaratna [65])

Dilated/spherical left atrium due to valvular disease, atrial fibrillation, or hypertension

CHA2DS2-VASc ¼ congestive heart failure, hypertension, age $75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65–74 years, sex category (female).

contractility (10). Recently, a consensus document

variable among individuals with AF and may be

proposed a classification of atrial cardiomyopathies (11).

associated with genetic factors/predisposition (21).

Idiopathic atrial cardiomyopathy is associated with

Notably, in some instances, AF may be a marker of

increased fibrosis, atrial arrhythmias, and impaired atrial

high atrial fibrosis burden rather than its cause (22).

function (11). Induced stiff LA syndrome after ablation,

Many cardiac conditions can lead to LA remodeling

estimated as occurring in approximately 2% to 8% of

that ultimately harbors AF. Ventricular- and valvular-

cases, has been related to decreased LA contractility and

mediated atrial remodeling includes a myriad of

compliance, with a direct correlation between scar

interstitial fibrosis, inflammation, myocyte hypertro-

burden and functional impairment (12,13). Atrial ischemia

phy, and necrosis, as well as glycogen accumulation.

may be a common, although underdiagnosed, cause of

Parallel to structural changes, impaired LA function is

atrial myopathy with impaired reservoir and booster-

the rule in most cases and carries with it an adverse

pump functions (14); it has been linked to increased

prognosis (23,24).

arrhythmic events (15), mitral regurgitation (14), and worse clinical outcomes (16). Atrial involvement in myocarditis may also be underestimated. Up to 30% of patients with myocarditis develop AF, and it may be a cause of atrial dysfunction (17).

MECHANISMS AND MANIFESTATIONS OF ATRIAL FAILURE Altered flow dynamics, suboptimal LV filling, and AF resulting from atrial failure may cause pulmonary

ATRIAL REMODELING. Atrial remodeling refers to

hypertension, HF, and increased thrombogenicity.

adverse electrophysiological, cellular, and structural

The presence of atrial failure may predispose a pa-

changes in atrial myocardial tissue in response to

tient to new-onset AF, which perpetuates and may

pressure and volume overload or arrhythmic insults.

even worsen a failing LA and its consequences in a

The main causes of LA remodeling include AF and

vicious circle (25). Therefore, we hypothesize that

ventricular/valve disease. Nevertheless, noncardiac

atrial failure, as happens with overt HF (26), activates

conditions, such as sleep apnea syndrome, hyper-

neurohormonal pathways (mainly of the renin-

tension, diabetes, and obesity, are important con-

angiotensin-aldosterone system and the sympathetic

tributors

nervous system), which may further impair atrial

to

LA

remodeling

through

different

pathways (18). Many conditions may coexist and

function (Central Illustration).

accelerate the adverse remodeling, driven in most

ATRIAL FAILURE AND RISK OF THROMBOEMBOLIC

cases by the presence of AF.

EVENTS. Embolic cardiovascular events have been

In addition to ion-channel changes and impaired

classically linked to an LAA source in the context of

electrophysiological properties, interstitial fibrosis is

AF, thus setting the rationale for surgical and

the hallmark of AF-induced LA remodeling and is

percutaneous LAA exclusion strategies. Recent evi-

associated with chamber dilation, spherical defor-

dence has challenged this assumption, providing

mation (19), and reduced atrial function (20), further

new insights into the existing link between atrial

promoting AF in a vicious circle (“AF begets AF”). The

disease and the risk of stroke independent of AF.

degree of structural tissue remodeling is highly

The lack of a robust association between the timing

225

226

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Atrial Failure

F I G U R E 1 Atrial Standstill

A I

B

C

132ms

II III aVR aVL aVF V1 V2 V3

Scar

V4 V5 V6 Healthy

Atrial and AV Dyssynchrony

↓ LV filling

Atrial Tissue Fibrosis

Atrial Standstill

Blood stasis

↓ Booster-pump

↓ Compliance

Endothelial dysfunction

Global HF & ↑ Risk Stroke Patient with a history of hypertension presenting with fatigue and dyspnea. Diagnostic workup revealed pathological P-wave duration (A), decreased left atrial (LA) function, absence of A waves in transmitral pulsed-Doppler echocardiography (B), and extensive fibrosis (Utah IV) detected by late gadolinium enhancement magnetic resonance imaging (C). The absence of significant ventricular abnormalities on magnetic resonance imaging and normal LA size suggest a primary atrial cardiomyopathy. AV ¼ atrioventricular; HF ¼ heart failure; LV ¼ left ventricular.

of AF episodes and stroke suggests that AF could be

and stroke (30,31). In addition, the amount of fibrosis

a marker of atrial myopathy rather than a cause of

in patients with stroke of unknown etiology is

thrombus formation (27). Current evidence for atrial

reportedly greater than in patients with an identified

myopathy promotes atrial substrate as an important

cause and comparable to those with AF (32). The link

cause of increased thrombogenicity, questioning the

between structural tissue abnormalities and a pro-

arrhythmia-mediated concept of thrombus forma-

thrombotic state is yet to be defined. Endothelial

tion alone as the leading cause of thromboembolic

damage and regional or global wall motion abnor-

stroke (28). Recent data from the MESA population

malities associated with increased fibrosis could

shows a strong association between LA reservoir

explain the increased risk of stroke (20,33).

function and incident embolic events, even after

The 3-dimensional asymmetrical configuration of

adjusting for established risk factors and presence

cardiac structures has beneficial effects in flow dy-

of documented AF (29).

namics. At the LA level, eccentric alignment with

In a highly selected AF population referred for

separate paths of left and right PV inflow and vortex

catheter ablation, LA structural remodeling has been

formation avoids blood stasis and redirects blood flow

associated with an increased risk of LAA thrombus

toward the mitral valve (conduit function) (5,34).

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Atrial Failure

VO 2 (40,41). Up to 45% of patients presenting with

T A B L E 2 Causes and Triggers of Atrial Failure

new-onset HF symptoms have LA dysfunction as the

A. Electrical Dyssynchrony
AV dyssynchrony o Left bundle branch block o First-degree AV block o Suboptimal pacemaker programming
Atrial dyssynchrony o Advanced interatrial block o Slow intra-atrial conduction velocities

underlying mechanism (42), suggesting that LA failure is an early driver in HFpEF syndrome and a crucial pathogenic factor. In addition to mechanical LA impairment driven by increased stiffness and pressure pulsatility (8), electrical atrial dysfunction and impaired LA-LV coupling could play a relevant

B. Booster-Pump and Reservoir Dysfunction
Fast/disorganized atrial activation o Atrial fibrillation o Focal/reentrant atrial tachycardia
Extensive atrial fibrosis o Advanced atrial remodeling o Extensive post-ablation scarring o Atrial infarction o Atrial cardiomyopathy

role in patients with HFpEF (43,45). Standalone atrial failure may cause HF symptoms, stroke, or pulmonary hypertension (29,40–42); however, atrial failure may more frequently worsen previously

asymptomatic

LV

dysfunction

and

decompensate or aggravate HF syndrome (Central

C. Impaired Conduit Function
Severe atrial dilation
Spherical atrial deformation
Altered transmitral pressure gradient

Illustration). At early stages of LV dysfunction, adaptive atrial chamber dilation accommodates higher preload without a significant increase in pulmonary wedge pressure; an increase in active pump function

AV [ atrioventricular.

contributes

to

maintaining

adequate

LV

filling

(Frank-Starling curve) (2,46). Progressive insults with Reduced peak velocity increases stasis in both the LA and LAA, alters vortical flow (as observed by 4-dimensional study in the LV), and facilitates thrombus formation (35,36). The diseased atrium may undergo geometric changes (spherical deformation) and chamber dilation, reducing the normal curvatures and asymmetry of the LA. These processes interfere with physiological flow dynamics (altered vortex formation), increasing blood stasis and stroke risk (37,38). Factors associated with atrial disease facilitate thrombus formation and increase the risk of stroke but are not exclusively linked to AF (Figure 3). In addition, stroke may further facilitate LA remodeling through

sympathetic

ganglionated

plexi,

activation leading

to

of LA

the

cardiac

endothelial

dysfunction and fibrosis (39).

increasing chamber dilation alter the conduit function as the first sign of atrial failure (41); nevertheless, a greater volume does not correspond to increased fiber shortening and contractility. Progressive impairment in global LA function fails to accommodate the excessive volume/pressure, leading to high LA and pulmonary wedge pressures and overt atrial failure syndrome. In the context of advanced tissue remodeling, development of AF is common, which further impairs electrical and mechanical LA function and has a deleterious effect on global cardiac performance, perpetuating a dangerous and vicious circle (47).

EXTRA-ATRIAL CONSEQUENCES OF ATRIAL FAILURE The deleterious effects of LV dysfunction on LA

ATRIAL AND VENTRICULAR INTERACTION IN HF.

structure and function are well defined; however,

Heart

fraction

the opposite interplay is less well characterized.

(HFpEF) is part of the HF spectrum. Abnormal LV

Some data suggest that AF promotes adverse ven-

diastolic function may be the substrate for HF in

tricular remodeling; preclinical histological and hu-

many patients, but in some instances HFpEF may be

man MRI studies have shown that the presence of

the consequence of a failing LA (40–42). Recent evi-

AF is associated with increased LV interstitial

dence suggests that LA function and remodeling are

fibrosis (47,48).

failure

with

preserved

ejection

independently associated with, or may precede, the

Ventricular dilation and altered systolic and dia-

onset of HF in an asymptomatic healthy population,

stolic function are common findings in studies of

as observed in a preclinical magnetic resonance im-

sustained rapid ventricular response to atrial ar-

aging (MRI) study (43,44). A reduced atrial reserve

rhythmias. At the histopathological level, the LV

during exercise may represent the first sign of a

myocardium exhibits inflammation, cardiomyocyte

failing LA in such a population. Compared with con-

morphological changes, and loss of the normal

trols, the only distinctive feature of patients with

myocardial extracellular matrix structure, composi-

HFpEF is reduced atrial reservoir and conduit capac-

tion, and function; this likely explains the increased

ity,

risk of HF and sudden cardiac death in these patients

which

independently

correlates

with

peak

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F I G U R E 2 Interatrial Block

Patient with ischemic cardiomyopathy and paroxysmal atrial fibrillation (AF) presenting with exercise intolerance. Electrocardiogram shows paced, prolonged P-wave duration of 190 ms with advanced interatrial block pattern (A). Transmitral pulsed-Doppler echocardiography shows normal filling pattern at rest (60 beats/min [bpm]); however, a progressive fusion of E and A waves is observed as heart rate increases (B). Note complete fusion of E and A waves at 100 beats/min, contributing to worsening of symptoms and global heart performance. Left atrial (LA) mapping revealed initial septal activation only, with no contribution of the interatrial Bachmann bundle and coronary sinus connections, with a long total LA activation time (C). Poor interatrial coupling and slow LA activation explain the markedly prolonged P-wave duration.

(49,50).

neurohormonal

remodeling and dysfunction and to determine the

pathways, including renin-angiotensin-aldosterone

Reactive

activation

of

point of no return from which recovery is unlikely

system and vasoactive peptides, may further pro-

despite suppression of arrhythmia.

mote adverse remodeling. Tachycardia-induced car-

Atrial rhythm and contraction contribute to effi-

diomyopathy may not be as “benign” and reversible

cient coronary blood flow. Irregular, shortened dias-

as initially thought; despite suppression of the causal

tole with an altered flow reserve induced by AF is a

atrial arrhythmia (not exclusively AF), LV dimensions

common cause of ventricular ischemia and type 2

and function, as well as T1 mapping values (a surro-

myocardial infarction (MI) (53). Patients with AF are

gate of diffuse interstitial fibrosis), do not normalize

at a 3-fold increased risk of MI, independent of other

in all patients (51,52). Further studies are needed to

risk factors. The coexistence of risk factors common

explore the broad spectrum of atrial-induced LV

to both entities, along with increased inflammation

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Atrial Failure

F I G U R E 3 Pathophysiology of Stroke in Atrial Failure

Valvular Ventricular cardiomyopathy Hypertension Sleep apnea syndrome Obesity Metabolic diseases

Atrial Cardiomyopathy

↑ Spherical deformation ↑ Dilation

Left Atrium Remodeling

↓ Reservoir/ Booster-pump

↑ Fibrosis

↑ Stasis

Endothelial dysfunction Wall motion abnormalities

Rhythm disorders

Endothelial dysfunction ↑ Stasis ↑ von Willebrand factor

Altered Vortex formation ↑ Stasis

Stroke

Functional, tissue, and electrical changes caused by primary or secondary atrial myopathy drive flow and endothelial and wall motion abnormalities, facilitating thrombus formation. The 4D atrial flow image is reproduced with permission from Föll et al. (67).

and platelet activation, are likely the drivers of this excess

risk.

Importantly,

anticoagulant

therapy

Atrial functional mitral and tricuspid regurgitation represent an atrial-induced valvular disease that may

seems to protect against incident MI in the AF pop-

produce or exacerbate HF and promote AF (56,57).

ulation (54). Ventricular MI due to atrial embolic

Rotation/displacement

source is a well-recognized cause of ischemia in AF

valvular plane and anterior tethering due to LA or RA

of

the

posterior

mitral

patients (55). As observed in patients with stroke,

dilation have been proposed as the main underlying

atrial dysfunction per se increases the risk of throm-

mechanisms (58). Recent data warning of the excess

boembolic events (29) and may eventually account

of mortality and incident HF associated with atrial

for embolic MI as well. Further studies are needed to

functional mitral regurgitation (59) suggest a poten-

provide a comprehensive evaluation of atrial me-

tial mechanism for the observed survival benefits of

chanical function in patients with MI of embolic

AF ablation in patients with HF. Could reduction in

origin.

AF burden improve atrial functional mitral and

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Atrial Failure

T A B L E 3 Diagnostic Strategies and Potential Interventions

Areas of Impact

Clinical Implications of Atrial Failure

Proposed Diagnostic Strategies

Potential Future Interventions

Risk of stroke

Identify non-AF individuals at risk of stroke Identify AF individuals at low risk of stroke

Atrial size/shape: MRI/CTA Fibrosis detection: MRI (LGE) Mechanical function: Echo, MRI (strain) Biomarkers

OAC might be indicated in individuals without AF or discouraged in patients with AF Upstream therapy to reduce fibrosis/thrombotic milieu

Heart failure

Identify mechanism of HF symptoms in the absence of LV abnormalities

Fibrosis detection: MRI (LGE) Mechanical function: Echo, MRI (strain) Quantification MR (Echo, MRI) Biomarkers

Tailored HF treatment Upstream therapy to reduce fibrosis Interventions to reduce MR Left atrial pacing

Mechanical LA dysfunction Atrial functional MR Atrial dyssynchrony AF management

Identify the arrhythmia mechanism Assess stage of atrial disease Assess likelihood of successful rhythm control

Atrial size/shape: MRI/CTA Fibrosis detection: MRI (LGE) Biomarkers

Tailored ablation approach (substrate-based vs. pulmonary vein isolation) Selection of candidates for rhythm or rate control

Dyssynchrony

Assess degree of interatrial and atrioventricular dyssynchrony

Right and left E/A (Echo)

Left atrial or bi-atrial pacing

Extra-atrial involvement

Assess LV abnormalities due to atrial failure Assess atrial functional MR Assess AF-driven functional TR

LV size and function: Echo, MRI Fibrosis detection: MRI (T1, LGE) Characterization of valvular insufficiency (Echo, MRI)

Sudden death risk stratification OAC indicated in advanced atrial failure to prevent embolic myocardial infarction AF suppression by ablation to improve MR/TR Interventions to reduce MR/TR (MitraClip, annuloplasty)

AF ¼ atrial fibrillation; CTA ¼ computed tomography angiography; HF ¼ heart failure; LA ¼ left atrium; LGE ¼ late gadolinium enhancement; LV ¼ left ventricle; MR ¼ mitral regurgitation; MRI ¼ magnetic resonance imaging; OAC ¼ oral anticoagulation; TR ¼ tricuspid regurgitation.

tricuspid regurgitation and prolong lifespan in this

CONCLUSIONS

population? Further studies are needed to explain this mechanism.

Atrial failure has emerged as a new entity defined as any atrial dysfunction causing impaired heart

DIAGNOSTIC STRATEGIES AND

performance, appearance of symptoms, and wors-

POTENTIAL INTERVENTIONS

ening quality of life or life expectancy, in the

Table 3 summarizes the main clinical aspects and implications of atrial failure, as well as the related diagnostic strategies and potential interventions. Atrial failure must be considered in the presence of compatible symptoms and any structural, functional, or electrical abnormalities of the LA not attributable to any other cardiac or extracardiac condition. Imaging results are key to determine LA function, detect atrial fibrosis, and assess blood flow patterns. Biomarkers are an emerging diagnostic and prognostic tool, with good performance to predict ischemic and bleeding risk (e.g., high-sensitivity troponin T, N-terminal pro–B-type natriuretic peptide, growth/ differentiation factor 15) (60), as well as fibrosis

absence of significant valvular or ventricular abnormalities. Recent advances in cardiac electrophysiology

and

imaging

have

improved

our

understanding of the highly complex atrial anatomy

and

function,

revealing

the

paramount

importance of the atria in optimal heart performance. It is time to reappraise the role of atrial dysfunction in the symptoms of many of our patients: marker, aggravating factor, consequence, or primary cause? Here, we propose the concept of atrial failure, which may foster basic and translational research to gain a better understanding of how to identify and manage atrial dysfunction in the 21st century.

burden or AF ablation success (microRNA miR-21)

ACKNOWLEDGMENTS The authors are grateful to

(61). Atrial voltage abnormalities may help to predict

Carolina Gálvez-Montón PhD, DVM, for the graphic

myocardial fibrosis,

impaired

LA

function, and

increased risk of stroke (62,63). Although any atrial

art contribution and Albert Teis for the support with cardiac imaging.

dysfunction in the context of compatible symptoms might be considered as atrial failure, establishing the

ADDRESS FOR CORRESPONDENCE: Dr. Felipe Bisbal,

development of a broad consensus. Acceptance of

Heart Institute - Hospital Universitari Germans Trias i

this concept will likely foster research in this field,

Pujol, Carretera Canyet s/n, 08916 Badalona, Barce-

and the term necessarily will be redefined with

lona, Spain. E-mail: [email protected]. Twitter:

greater precision as we gain more knowledge.

@bisbal_EP, @adribaran.

appropriate

diagnostic

criteria

will

require

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KEY WORDS atrial failure, atrial fibrillation, atrial function, heart failure, interatrial block, stroke