REVIEW URRENT C OPINION
Left atrium function in patients with coronary artery disease Emanuela Facchini, Anna Degiovanni, and Paolo N. Marino
Purpose of review The left atrial cavity has recently been identified as a potential biomarker for cardiac and cerebrovascular accidents. This review examines the potential of left atrial size and function in predicting cardiovascular disease in the general population and outcomes in coronary artery disease (CAD) patients. Recent findings The atrium is perfused primarily by branches of the proximal left circumflex coronary artery (LCx), and depression of the cavity mechanical performance has been demonstrated in experimental studies during LCx occlusion. Thus, left atrial volume and function assessment may have prognostic relevance, particularly in CAD patients. Such a line of thinking, however, is challenged by the widespread notion that the contribution by left atrial chamber morphology and functional quantitation to the risk stratification process after a first cardiovascular event is not adequately considered. However, a number of studies have shown that left atrial volume predicts survival and major adverse events after an acute myocardial infarction. Left atrial remodeling also provides an important overall prognostic information and correlates with brain natriuretic peptide after primary percutaneous coronary interventions. Summary Evaluation of left atrial size and function is currently of great interest and it will be more so in the very near future, given its potential for insights into the pathophysiology of the ischemic heart, which makes it an important clinical risk identifier in CAD patients. Keywords ischemic heart disease, left atrium function, left atrium volume
INTRODUCTION The left atrium exerts multiple functions, acting as a reservoir during left ventricular systole, as a conduit for blood flowing from the lungs to the left ventricular cavity during diastole, as an active contractile chamber after atrial electrical activation and as a volume sensor for the heart by releasing natriuretic peptides [1,2]. In recent years, a growing body of evidence has developed suggesting that left atrial size and function are markers of adverse cardiovascular outcomes and cerebrovascular accidents [3 ]. This review examines the ability of left atrial size and function to detect cardiovascular diseases and predict outcomes within the general population and, in particular, in coronary artery disease (CAD) patients. &&
PATHOPHYSIOLOGIC DETERMINANTS: LEFT ATRIAL SIZE AS A DESCRIPTOR OF LEFT VENTRICULAR DIASTOLIC STATUS During ventricular diastole, the atrial cavity is directly exposed to left ventricular pressures. With
worsening left ventricular compliance, left atrial pressure increases so as to maintain adequate left ventricular filling, which results in left atrial enlargement [4]. Therefore, left atrial volume may potentially reflect the severity of the underlying diastolic left ventricular dysfunction. Left atrial remodeling may also describe the chronic exposure to the increased left ventricular filling pressures [5]. Thus, left atrial volume, as a marker of severity and duration of diastolic dysfunction, can provide incremental prognostic information, as compared with that provided by Department of Translational Medicine, Clinical Cardiology, Universita` del Piemonte Orientale, Azienda Ospedaliero Universitaria ‘Maggiore della Carita`’, Novara, Italy Correspondence to Prof. Paolo N. Marino, FESC, FACC, Director, Clinical Cardiology, Department of Translational Medicine, Azienda Ospedaliero Universitaria ‘Maggiore della Carita`’, Universita` del Piemonte Orientale, Corso Mazzini 18, 28100 Novara, Italy. Tel: +39 0 321 3733597; fax: +3733407; e-mail: [email protected] Curr Opin Cardiol 2014, 29:423–429 DOI:10.1097/HCO.0000000000000085
0268-4705 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-cardiology.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Imaging and echocardiography
KEY POINTS Left atrial contribution to left ventricular filling is different during LAD vs. LCx occlusion because left atrium is perfused primarily by LCx. Left atrial volume ‘weight’ in the prediction of development of ischemic events in the general population is not widely recognized. Left atrial volume and function predict survival after an acute MI and after a primary percutaneous coronary intervention. Left atrial abnormalities can be of some help in myocardial perfusion study interpretation among patients with left ventricular hypertrophy. Left atrial strain measurements can be a helpful method to evaluate the extent of ventricular derangement in acutely infarcted patients.
multiple load-dependent Doppler parameters reflective of instantaneous left ventricular diastolic function and filling pressures [6]. Left atrial volume, in fact, has been termed ‘glycosylated hemoglobin of diastolic dysfunction’ [6], mimicking the role of such a laboratory marker vs. the glycemic control in diabetes. Furthermore, the atrial cavity acts as a volume sensor of the heart, which reacts by producing cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)]. These polypeptide hormones, mainly produced by atrial cardiocytes, reflect wall response to stretch [2] and are also associated with poorer CAD prognosis [7].
The prognostic added value of atrial remodeling Due to the opposing effects of preload and compliance on transmitral velocities, the mitral inflow pattern may appear normal (pseudonormal) despite abnormal filling pressures [8]. In such a scenario, left atrial volume index provides the highest discriminative added value, helping to differentiate between normal and pseudonormal transmitral flow profiles [5]. Therefore, assessment of acute (Doppler echocardiographic parameters) and chronic (left atrial volume) diastolic dysfunction indexes provide a powerful tool for distinguishing between normal subjects and patients with cardiovascular diseases. Left atrial phasic functions change as well, with reservoir and conduit reciprocating with increasing degrees of diastolic dysfunction, whereas pump function, facing the increasing resistance to left ventricular filling, progressively decreases [9]. 424
www.co-cardiology.com
Pritchett et al. [10] demonstrated that by incorporating diastolic dysfunction metrics, obtained by using Doppler ultrasounds applied to the general population, the correlation between left atrial volume (and its independent predictors including left ventricular mass and ejection fraction) and presence of cardiovascular diseases increased.
The more informative value of minimum vs. maximum atrial volume The relationship between left atrial minimum volume and diastolic function has been investigated in a limited number of studies [11,12]. Russo et al. [11] demonstrated that left atrial minimum volume (direct relation) and the reservoir function (inverse relation) are better correlates of left ventricular diastolic function than left atrial maximum volume. The minimum volume is measured at end-diastole, after the cavity has been exposed to left ventricular diastolic pressure (therefore accounting for atrial afterload) and it is not influenced by systolic events, which contribute to affect maximum volume in end-systole. Thus, the increase in left atrial minimum volume with worsening diastolic function can be more informative than that of left atrial maximum volume while being already evident in the early stage of diastolic dysfunction [11]. For the same end-diastolic left atrial volume, in fact, a larger left atrial maximum volume may simply be the expression of a stronger longitudinal ventricular shortening, rather than reflective of a worsened diastole [13 ]. Such findings, together with the greater ability to predict atrial arrhythmias observed in some studies, suggest that left atrial minimum volume may be a better marker of left atrial function and cavity remodeling than left atrial maximum volume [11]. &
LEFT ATRIUM AND CORONARY ARTERY DISEASE: HUMAN AND EXPERIMENTAL MODELS The capacity of distinguishing, from atrial data, which one, among the various coronary vessels, is primarily involved in a given CAD patient is real because the human left atrial cavity is perfused primarily by branches of the proximal left circumflex coronary artery (LCx), with smaller contributions from the right coronary artery, whereas the left anterior descending (LAD) does not perfuse the atrium at all [14]. Therefore, during left ventricular ischemia, the atrial contribution to left ventricular filling during LAD occlusion is likely to be different from the one occurring during proximal LCx occlusion [15]. Volume 29 Number 5 September 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Left atrium function in patients with CAD Facchini et al.
Left atrial systolic and diastolic functions have been analyzed in an animal model of acute left ventricular ischemia obtained by proximal LCx artery occlusion, as opposed to a condition without atrial ischemia following mid-LAD coronary artery ligation (seven sheep in each group) [16]. Left atrial pressures and volumes were simultaneously recorded using a pressure catheter and real-time three-dimensional echocardiography, respectively. Left atrial stroke volume contributed 63% of left ventricular stroke volume during LAD coronary artery occlusion, but only 32% during LCx coronary artery ligation. This experimental study is compatible with a dramatic depression of left atrial pump function during proximal LCx, as opposed to LAD coronary artery occlusion (Table 1) [16], confirming the differential contribution of the various coronary vessels to left atrial mechanical performance. Yan et al. [17] measured global and regional systolic and diastolic left atrial longitudinal deformation using velocity vector imaging in 60 patients with CAD (defined as >50% lumen narrowing of at least one major coronary vessel) and 25 controls. They excluded patients with myocardial infarction (MI) or history of coronary revascularization. As compared with controls and patients with singlevessel disease other than LAD coronary artery, left atrial longitudinal strain rate during atrial contraction was significantly increased among patients exhibiting LAD involvement, whereas no similar finding was evident in patients with LCx/right coronary artery (RCA) stenosis, possibly because of atrial ischemia caused by obstructive LCx/RCA branches that supply the atrium. Stefanadis et al. [15] compared left atrial function in 32 patients with LAD and LCx coronary artery stenosis at rest and immediately after pacing-induced tachycardia or during coronary occlusion. In patients with LAD stenosis, left ventricular supply or demand ischemia was associated with enhanced left atrial pump function quantified by left atrial pressure–area relations (derived from simultaneous double-tip micromanometer pressure
recordings and automatic boundary detection echocardiograms). Similarly, Sigwart et al. [18] noted augmentation of left atrial stroke volume and ratio of contribution of left atrial contraction to left ventricular stroke volume index in 32 patients 30 s after LAD occlusion. In conclusion, in patients with LAD disease, there is an inverse relation between left ventricular and left atrial performance. While ventricular stroke work decreases, atrial stroke work increases significantly. Such behavior has to be interpreted as the atrial response to increased preload and afterload imposed by the stiff, dilated ventricle. In contrast, in patients with proximal LCx disease, both the left ventricular and left atrial cavity suffer from ischemia. Thus, we can conclude that left atrial function plays an important role in maintaining overall cardiac performance during left ventricular ischemia in patients with a significant LAD stenosis, whereas this is not necessarily true when the LCx/RCA complex is involved.
LEFT ATRIAL SIZE AND FUNCTION AS A PROGNOSTIC MARKER IN CORONARY ARTERY DISESAE Left atrial volume and function assessment may predict cardiovascular disease in the general population and be a prognostic marker in CAD patients.
Left atrial volume as a predictor of coronary artery disease Indexes of left atrial size are markers of cardiovascular risk in the general population according to studies that have examined their prognostic value in cardiac events’ risk stratification [19], although the atrial volume ‘weight’ in the prediction of subsequent development of ischemic events is, presently, not widely recognized. Tsang et al. [20] analyzed a selected population of 1160 persons aged 65 years or older in sinus rhythm without significant valvular disease. Indexed left atrial volume, together
Table 1. Left atrial function at baseline and during LAD and LCx occlusion LCx group Baseline Left atrial stroke volume (ml) Left atrial ejection fraction (%) Left atrial stroke work (mmHg/ml) Atrial to ventricular stroke volume ratio (%)
LAD group Occlusion
8.5 4
4.9 2a
27 9
a
17.7 8 46 20
10 4
9.3 7a,b 32 19a,b
Baseline 7.7 3
Occlusion 13.1 5a
33 10 17.8 15
39 1 31.6 19a
39 15
63 18a
Adapted from Bauer et al. [16]. LAD, left anterior descending; LCx, circumflex coronary artery. a P < 0.05 occlusion vs. baseline. b P < 0.05 LAD occlusion vs. LCx occlusion.
0268-4705 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
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425
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Imaging and echocardiography
with other traditional risk factors, acted as an independent predictor of revascularization and MI. Similarly, in an even larger general population (45 years, n ¼ 2042), left atrial dimension and volume were associated with a history of CAD and MI [10]. A similar predictive value of left atrial volume for the subsequent development of MI was also observed by Osranek et al. [21] in a smaller population study (n ¼ 46) performed in patients with lone atrial fibrillation. In contrast, results from the Cardiovascular Health Study [22] suggested that increased M-mode-derived left atrial dimension was not independently associated with the development of CAD in people older than 65 years (n ¼ 5888) after adjustments for left ventricular mass and other traditional cardiovascular risk factors. Nawathe et al. [23 ] prospectively investigated the relation between left ventricular hypertrophy and left atrial abnormality among 78 patients undergoing a myocardial perfusion study with severity of myocardial perfusion study defect (SPECT). In the 48 patients who had a positive myocardial perfusion imaging result, left atrial size was significantly increased. The differential change in left atrial size was greatest when the myocardial perfusion study defect exceeded moderate severity. So, the presence of left atrial abnormalities may be of some help in the myocardial perfusion study interpretation among patients with left ventricular hypertrophy, wherein such markers appear to correlate with the severity of the myocardial perfusion study defect (Fig. 1) [23 ], and likely acts as predictors of cardiac events also in the general population. &&
&&
Left atrial size and function vs. outcome in acute coronary syndromes: short-term prediction Acute MI can modulate not only systolic but also diastolic left ventricular dysfunction. During the
50
No defect
Mild
Moderate
Severe
LA size
45 44±5
40
38±5 36±5
35±4
35 30 0
1
2
3
Myocardial perfusion imaging defect
4 p < 0.0001
FIGURE 1. The progressive increment in left atrial size vs. severity of the myocardial perfusion imaging defect as obtained by SPECT in patients with ventricular hypertrophy. Adapted from Nawathe et al. [23 ]. &&
426
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early phases of an acute MI, 38% of patients have impaired relaxation and 24% have a restrictive filling pattern [24]. The important consequence of diastolic dysfunction is the elevation of left ventricular filling pressures [25]. Left ventricular diastolic dysfunction has been related to morbidity and death independently of systolic function derangement in acute MI [26,27]. Thus, diastole and left ventricular filling pressures could be used as prognostic markers after an acute cardiac necrotic insult [3 ]. A number of studies have shown that left atrial volume also predicts survival after an acute MI. Truong et al. [28] performed 64-slice computed tomography (CT) for diagnosing CAD and derived left atrial volumes and indices in 377 emergency department patients with chest pain. People with cardiac risk factors or CAD by CT exhibited a bigger atrium. Jing et al. [29 ] measured left atrial and left ventricular global longitudinal strain rate (GLSR) by two-dimensional speckle tracking echocardiography in 50 patients with non ST-segment elevation MI (NSTEMI) and 40 age-matched normal controls [29 ]. Compared with healthy subjects, NSTEMI patients had significantly increased left atrial volumes, but significantly decreased left atrial GLSR. Global left atrial peak negative strain rate during early ventricular diastole was significantly correlated with left ventricular contractile function. ¨hl et al. [30] measured left atrial size and Ku function from coronary CT in 384 NSTEMI patients. After adjustments for age, number of diseased coronary arteries, left ventricular ejection fraction and Killip class, both left atrial fractional change (calculated as the difference between left atrial maximum and minimal volume divided by left atrial maximal volume) and atrial pump function (defined as left atrial stroke volume divided by the left atrial volume just before atrial systole) resulted as significant independent predictors of all-cause mortality, but not left atrial maximum volume. Thus, in a low-risk group of patients with NSTEMI, reduced left atrial function provides prognostic value incremental to that of left atrial maximal volume. In another study, baseline atrial functional variables, collected within the first 72 h of admission, were measured in 164 NSTEMI patients [31]. Tissue Doppler imaging measurement of mean left atrial conduction velocity was an independent predictor for recurrence of an acute coronary syndrome or congestive heart failure (CHF) and it was incremental to clinical data, ventricular pump performance and left ventricular diastolic function assessment for predicting events at 6-month follow-up. Finally, in 314 patients with MI followed for a mean of 15 months, left atrial volume more than 32 ml/m2 was a powerful predictor for all-cause &&
&
&
Volume 29 Number 5 September 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Left atrium function in patients with CAD Facchini et al.
mortality and was incremental to clinical information and left ventricular function data [32]. Baseline left atrial size was also an independent predictor of death or CHF hospitalization in 640 patients following high-risk MI (with left ventricular dysfunction and/or CHF). Moreover, left atrial remodeling during the first month (early left atrial remodeling) after an acute high-risk MI was associated with an adverse outcome [33].
Left atrial size and function vs. outcome in acute coronary syndromes: long-term prediction Beinart et al. [34] reported that, in patients with acute MI, increased left atrial volume more than 32 ml/m2 (n ¼ 68), quantified within the first 48 h from admission, is an independent predictor of 5-year mortality when compared with patients (n ¼ 72) with smaller atria. In 199 patients in whom a cardiac resonance magnetic study was performed within 1–3 days from an MI, left atrial maximum and minimal volume and left atrial function descriptors independently predicted major adverse cardiac events and provided incremental prognostic information beyond maximum cavity volume over 2.3-year follow-up [35 ]. Similarly, in 320 patients with an acute MI, left atrial volume and performance (mechanical function and systolic strain) measured within 48 h were independently associated with an adverse outcome (all-cause mortality, reinfarction and CHF hospitalization) after adjustment for clinical and echocardiographic parameters and followed for a mean of 27 months [36]. In 843 patients, peak left atrial longitudinal strain, prospectively measured within 48 h of MI admission, was significantly related to the composite outcome of death and CHF during a follow-up lasting for a median of 23 months [13 ]. However, this effect did not persist after adjustment for global left ventricular longitudinal strain, maximum left atrial volume and age, suggesting that peak left atrial longitudinal strain represents a composite of longitudinal left ventricular systolic function and maximum atrial volume. Finally, in 253 acute MI patients undergoing primary percutaneous coronary interventions (PCI), Cho et al. [37] analyzed left atrial volume changes over a long-term clinical follow-up (30.8 7.5 months). An incremental change in volume of the left atrial cavity was an independent predictor of new-onset atrial fibrillation or CHF hospitalization (Table 2) [37]. Patients who survived the 12-month period showed an overall increase in left atrial volume of 1.86 þ 4 .01 ml/m2. The patients’ group displaying an increased left atrial volume exhibited low left ventricular ejection fraction, large &
Table 2. New-onset atrial fibrillation or hospitalization with heart failure according to changes in LAVI after a primary percutaneous coronary intervention Decreased LAVI (%)
Increased LAVI (%)
P value
Hospitalization with heart failure
1.80
17.60
Left atrium function in patients with coronary artery disease Emanuela Facchini, Anna Degiovanni, and Paolo N. Marino
Purpose of review The left atrial cavity has recently been identified as a potential biomarker for cardiac and cerebrovascular accidents. This review examines the potential of left atrial size and function in predicting cardiovascular disease in the general population and outcomes in coronary artery disease (CAD) patients. Recent findings The atrium is perfused primarily by branches of the proximal left circumflex coronary artery (LCx), and depression of the cavity mechanical performance has been demonstrated in experimental studies during LCx occlusion. Thus, left atrial volume and function assessment may have prognostic relevance, particularly in CAD patients. Such a line of thinking, however, is challenged by the widespread notion that the contribution by left atrial chamber morphology and functional quantitation to the risk stratification process after a first cardiovascular event is not adequately considered. However, a number of studies have shown that left atrial volume predicts survival and major adverse events after an acute myocardial infarction. Left atrial remodeling also provides an important overall prognostic information and correlates with brain natriuretic peptide after primary percutaneous coronary interventions. Summary Evaluation of left atrial size and function is currently of great interest and it will be more so in the very near future, given its potential for insights into the pathophysiology of the ischemic heart, which makes it an important clinical risk identifier in CAD patients. Keywords ischemic heart disease, left atrium function, left atrium volume
INTRODUCTION The left atrium exerts multiple functions, acting as a reservoir during left ventricular systole, as a conduit for blood flowing from the lungs to the left ventricular cavity during diastole, as an active contractile chamber after atrial electrical activation and as a volume sensor for the heart by releasing natriuretic peptides [1,2]. In recent years, a growing body of evidence has developed suggesting that left atrial size and function are markers of adverse cardiovascular outcomes and cerebrovascular accidents [3 ]. This review examines the ability of left atrial size and function to detect cardiovascular diseases and predict outcomes within the general population and, in particular, in coronary artery disease (CAD) patients. &&
PATHOPHYSIOLOGIC DETERMINANTS: LEFT ATRIAL SIZE AS A DESCRIPTOR OF LEFT VENTRICULAR DIASTOLIC STATUS During ventricular diastole, the atrial cavity is directly exposed to left ventricular pressures. With
worsening left ventricular compliance, left atrial pressure increases so as to maintain adequate left ventricular filling, which results in left atrial enlargement [4]. Therefore, left atrial volume may potentially reflect the severity of the underlying diastolic left ventricular dysfunction. Left atrial remodeling may also describe the chronic exposure to the increased left ventricular filling pressures [5]. Thus, left atrial volume, as a marker of severity and duration of diastolic dysfunction, can provide incremental prognostic information, as compared with that provided by Department of Translational Medicine, Clinical Cardiology, Universita` del Piemonte Orientale, Azienda Ospedaliero Universitaria ‘Maggiore della Carita`’, Novara, Italy Correspondence to Prof. Paolo N. Marino, FESC, FACC, Director, Clinical Cardiology, Department of Translational Medicine, Azienda Ospedaliero Universitaria ‘Maggiore della Carita`’, Universita` del Piemonte Orientale, Corso Mazzini 18, 28100 Novara, Italy. Tel: +39 0 321 3733597; fax: +3733407; e-mail: [email protected] Curr Opin Cardiol 2014, 29:423–429 DOI:10.1097/HCO.0000000000000085
0268-4705 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-cardiology.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Imaging and echocardiography
KEY POINTS Left atrial contribution to left ventricular filling is different during LAD vs. LCx occlusion because left atrium is perfused primarily by LCx. Left atrial volume ‘weight’ in the prediction of development of ischemic events in the general population is not widely recognized. Left atrial volume and function predict survival after an acute MI and after a primary percutaneous coronary intervention. Left atrial abnormalities can be of some help in myocardial perfusion study interpretation among patients with left ventricular hypertrophy. Left atrial strain measurements can be a helpful method to evaluate the extent of ventricular derangement in acutely infarcted patients.
multiple load-dependent Doppler parameters reflective of instantaneous left ventricular diastolic function and filling pressures [6]. Left atrial volume, in fact, has been termed ‘glycosylated hemoglobin of diastolic dysfunction’ [6], mimicking the role of such a laboratory marker vs. the glycemic control in diabetes. Furthermore, the atrial cavity acts as a volume sensor of the heart, which reacts by producing cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)]. These polypeptide hormones, mainly produced by atrial cardiocytes, reflect wall response to stretch [2] and are also associated with poorer CAD prognosis [7].
The prognostic added value of atrial remodeling Due to the opposing effects of preload and compliance on transmitral velocities, the mitral inflow pattern may appear normal (pseudonormal) despite abnormal filling pressures [8]. In such a scenario, left atrial volume index provides the highest discriminative added value, helping to differentiate between normal and pseudonormal transmitral flow profiles [5]. Therefore, assessment of acute (Doppler echocardiographic parameters) and chronic (left atrial volume) diastolic dysfunction indexes provide a powerful tool for distinguishing between normal subjects and patients with cardiovascular diseases. Left atrial phasic functions change as well, with reservoir and conduit reciprocating with increasing degrees of diastolic dysfunction, whereas pump function, facing the increasing resistance to left ventricular filling, progressively decreases [9]. 424
www.co-cardiology.com
Pritchett et al. [10] demonstrated that by incorporating diastolic dysfunction metrics, obtained by using Doppler ultrasounds applied to the general population, the correlation between left atrial volume (and its independent predictors including left ventricular mass and ejection fraction) and presence of cardiovascular diseases increased.
The more informative value of minimum vs. maximum atrial volume The relationship between left atrial minimum volume and diastolic function has been investigated in a limited number of studies [11,12]. Russo et al. [11] demonstrated that left atrial minimum volume (direct relation) and the reservoir function (inverse relation) are better correlates of left ventricular diastolic function than left atrial maximum volume. The minimum volume is measured at end-diastole, after the cavity has been exposed to left ventricular diastolic pressure (therefore accounting for atrial afterload) and it is not influenced by systolic events, which contribute to affect maximum volume in end-systole. Thus, the increase in left atrial minimum volume with worsening diastolic function can be more informative than that of left atrial maximum volume while being already evident in the early stage of diastolic dysfunction [11]. For the same end-diastolic left atrial volume, in fact, a larger left atrial maximum volume may simply be the expression of a stronger longitudinal ventricular shortening, rather than reflective of a worsened diastole [13 ]. Such findings, together with the greater ability to predict atrial arrhythmias observed in some studies, suggest that left atrial minimum volume may be a better marker of left atrial function and cavity remodeling than left atrial maximum volume [11]. &
LEFT ATRIUM AND CORONARY ARTERY DISEASE: HUMAN AND EXPERIMENTAL MODELS The capacity of distinguishing, from atrial data, which one, among the various coronary vessels, is primarily involved in a given CAD patient is real because the human left atrial cavity is perfused primarily by branches of the proximal left circumflex coronary artery (LCx), with smaller contributions from the right coronary artery, whereas the left anterior descending (LAD) does not perfuse the atrium at all [14]. Therefore, during left ventricular ischemia, the atrial contribution to left ventricular filling during LAD occlusion is likely to be different from the one occurring during proximal LCx occlusion [15]. Volume 29 Number 5 September 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Left atrium function in patients with CAD Facchini et al.
Left atrial systolic and diastolic functions have been analyzed in an animal model of acute left ventricular ischemia obtained by proximal LCx artery occlusion, as opposed to a condition without atrial ischemia following mid-LAD coronary artery ligation (seven sheep in each group) [16]. Left atrial pressures and volumes were simultaneously recorded using a pressure catheter and real-time three-dimensional echocardiography, respectively. Left atrial stroke volume contributed 63% of left ventricular stroke volume during LAD coronary artery occlusion, but only 32% during LCx coronary artery ligation. This experimental study is compatible with a dramatic depression of left atrial pump function during proximal LCx, as opposed to LAD coronary artery occlusion (Table 1) [16], confirming the differential contribution of the various coronary vessels to left atrial mechanical performance. Yan et al. [17] measured global and regional systolic and diastolic left atrial longitudinal deformation using velocity vector imaging in 60 patients with CAD (defined as >50% lumen narrowing of at least one major coronary vessel) and 25 controls. They excluded patients with myocardial infarction (MI) or history of coronary revascularization. As compared with controls and patients with singlevessel disease other than LAD coronary artery, left atrial longitudinal strain rate during atrial contraction was significantly increased among patients exhibiting LAD involvement, whereas no similar finding was evident in patients with LCx/right coronary artery (RCA) stenosis, possibly because of atrial ischemia caused by obstructive LCx/RCA branches that supply the atrium. Stefanadis et al. [15] compared left atrial function in 32 patients with LAD and LCx coronary artery stenosis at rest and immediately after pacing-induced tachycardia or during coronary occlusion. In patients with LAD stenosis, left ventricular supply or demand ischemia was associated with enhanced left atrial pump function quantified by left atrial pressure–area relations (derived from simultaneous double-tip micromanometer pressure
recordings and automatic boundary detection echocardiograms). Similarly, Sigwart et al. [18] noted augmentation of left atrial stroke volume and ratio of contribution of left atrial contraction to left ventricular stroke volume index in 32 patients 30 s after LAD occlusion. In conclusion, in patients with LAD disease, there is an inverse relation between left ventricular and left atrial performance. While ventricular stroke work decreases, atrial stroke work increases significantly. Such behavior has to be interpreted as the atrial response to increased preload and afterload imposed by the stiff, dilated ventricle. In contrast, in patients with proximal LCx disease, both the left ventricular and left atrial cavity suffer from ischemia. Thus, we can conclude that left atrial function plays an important role in maintaining overall cardiac performance during left ventricular ischemia in patients with a significant LAD stenosis, whereas this is not necessarily true when the LCx/RCA complex is involved.
LEFT ATRIAL SIZE AND FUNCTION AS A PROGNOSTIC MARKER IN CORONARY ARTERY DISESAE Left atrial volume and function assessment may predict cardiovascular disease in the general population and be a prognostic marker in CAD patients.
Left atrial volume as a predictor of coronary artery disease Indexes of left atrial size are markers of cardiovascular risk in the general population according to studies that have examined their prognostic value in cardiac events’ risk stratification [19], although the atrial volume ‘weight’ in the prediction of subsequent development of ischemic events is, presently, not widely recognized. Tsang et al. [20] analyzed a selected population of 1160 persons aged 65 years or older in sinus rhythm without significant valvular disease. Indexed left atrial volume, together
Table 1. Left atrial function at baseline and during LAD and LCx occlusion LCx group Baseline Left atrial stroke volume (ml) Left atrial ejection fraction (%) Left atrial stroke work (mmHg/ml) Atrial to ventricular stroke volume ratio (%)
LAD group Occlusion
8.5 4
4.9 2a
27 9
a
17.7 8 46 20
10 4
9.3 7a,b 32 19a,b
Baseline 7.7 3
Occlusion 13.1 5a
33 10 17.8 15
39 1 31.6 19a
39 15
63 18a
Adapted from Bauer et al. [16]. LAD, left anterior descending; LCx, circumflex coronary artery. a P < 0.05 occlusion vs. baseline. b P < 0.05 LAD occlusion vs. LCx occlusion.
0268-4705 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
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425
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Imaging and echocardiography
with other traditional risk factors, acted as an independent predictor of revascularization and MI. Similarly, in an even larger general population (45 years, n ¼ 2042), left atrial dimension and volume were associated with a history of CAD and MI [10]. A similar predictive value of left atrial volume for the subsequent development of MI was also observed by Osranek et al. [21] in a smaller population study (n ¼ 46) performed in patients with lone atrial fibrillation. In contrast, results from the Cardiovascular Health Study [22] suggested that increased M-mode-derived left atrial dimension was not independently associated with the development of CAD in people older than 65 years (n ¼ 5888) after adjustments for left ventricular mass and other traditional cardiovascular risk factors. Nawathe et al. [23 ] prospectively investigated the relation between left ventricular hypertrophy and left atrial abnormality among 78 patients undergoing a myocardial perfusion study with severity of myocardial perfusion study defect (SPECT). In the 48 patients who had a positive myocardial perfusion imaging result, left atrial size was significantly increased. The differential change in left atrial size was greatest when the myocardial perfusion study defect exceeded moderate severity. So, the presence of left atrial abnormalities may be of some help in the myocardial perfusion study interpretation among patients with left ventricular hypertrophy, wherein such markers appear to correlate with the severity of the myocardial perfusion study defect (Fig. 1) [23 ], and likely acts as predictors of cardiac events also in the general population. &&
&&
Left atrial size and function vs. outcome in acute coronary syndromes: short-term prediction Acute MI can modulate not only systolic but also diastolic left ventricular dysfunction. During the
50
No defect
Mild
Moderate
Severe
LA size
45 44±5
40
38±5 36±5
35±4
35 30 0
1
2
3
Myocardial perfusion imaging defect
4 p < 0.0001
FIGURE 1. The progressive increment in left atrial size vs. severity of the myocardial perfusion imaging defect as obtained by SPECT in patients with ventricular hypertrophy. Adapted from Nawathe et al. [23 ]. &&
426
www.co-cardiology.com
early phases of an acute MI, 38% of patients have impaired relaxation and 24% have a restrictive filling pattern [24]. The important consequence of diastolic dysfunction is the elevation of left ventricular filling pressures [25]. Left ventricular diastolic dysfunction has been related to morbidity and death independently of systolic function derangement in acute MI [26,27]. Thus, diastole and left ventricular filling pressures could be used as prognostic markers after an acute cardiac necrotic insult [3 ]. A number of studies have shown that left atrial volume also predicts survival after an acute MI. Truong et al. [28] performed 64-slice computed tomography (CT) for diagnosing CAD and derived left atrial volumes and indices in 377 emergency department patients with chest pain. People with cardiac risk factors or CAD by CT exhibited a bigger atrium. Jing et al. [29 ] measured left atrial and left ventricular global longitudinal strain rate (GLSR) by two-dimensional speckle tracking echocardiography in 50 patients with non ST-segment elevation MI (NSTEMI) and 40 age-matched normal controls [29 ]. Compared with healthy subjects, NSTEMI patients had significantly increased left atrial volumes, but significantly decreased left atrial GLSR. Global left atrial peak negative strain rate during early ventricular diastole was significantly correlated with left ventricular contractile function. ¨hl et al. [30] measured left atrial size and Ku function from coronary CT in 384 NSTEMI patients. After adjustments for age, number of diseased coronary arteries, left ventricular ejection fraction and Killip class, both left atrial fractional change (calculated as the difference between left atrial maximum and minimal volume divided by left atrial maximal volume) and atrial pump function (defined as left atrial stroke volume divided by the left atrial volume just before atrial systole) resulted as significant independent predictors of all-cause mortality, but not left atrial maximum volume. Thus, in a low-risk group of patients with NSTEMI, reduced left atrial function provides prognostic value incremental to that of left atrial maximal volume. In another study, baseline atrial functional variables, collected within the first 72 h of admission, were measured in 164 NSTEMI patients [31]. Tissue Doppler imaging measurement of mean left atrial conduction velocity was an independent predictor for recurrence of an acute coronary syndrome or congestive heart failure (CHF) and it was incremental to clinical data, ventricular pump performance and left ventricular diastolic function assessment for predicting events at 6-month follow-up. Finally, in 314 patients with MI followed for a mean of 15 months, left atrial volume more than 32 ml/m2 was a powerful predictor for all-cause &&
&
&
Volume 29 Number 5 September 2014
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Left atrium function in patients with CAD Facchini et al.
mortality and was incremental to clinical information and left ventricular function data [32]. Baseline left atrial size was also an independent predictor of death or CHF hospitalization in 640 patients following high-risk MI (with left ventricular dysfunction and/or CHF). Moreover, left atrial remodeling during the first month (early left atrial remodeling) after an acute high-risk MI was associated with an adverse outcome [33].
Left atrial size and function vs. outcome in acute coronary syndromes: long-term prediction Beinart et al. [34] reported that, in patients with acute MI, increased left atrial volume more than 32 ml/m2 (n ¼ 68), quantified within the first 48 h from admission, is an independent predictor of 5-year mortality when compared with patients (n ¼ 72) with smaller atria. In 199 patients in whom a cardiac resonance magnetic study was performed within 1–3 days from an MI, left atrial maximum and minimal volume and left atrial function descriptors independently predicted major adverse cardiac events and provided incremental prognostic information beyond maximum cavity volume over 2.3-year follow-up [35 ]. Similarly, in 320 patients with an acute MI, left atrial volume and performance (mechanical function and systolic strain) measured within 48 h were independently associated with an adverse outcome (all-cause mortality, reinfarction and CHF hospitalization) after adjustment for clinical and echocardiographic parameters and followed for a mean of 27 months [36]. In 843 patients, peak left atrial longitudinal strain, prospectively measured within 48 h of MI admission, was significantly related to the composite outcome of death and CHF during a follow-up lasting for a median of 23 months [13 ]. However, this effect did not persist after adjustment for global left ventricular longitudinal strain, maximum left atrial volume and age, suggesting that peak left atrial longitudinal strain represents a composite of longitudinal left ventricular systolic function and maximum atrial volume. Finally, in 253 acute MI patients undergoing primary percutaneous coronary interventions (PCI), Cho et al. [37] analyzed left atrial volume changes over a long-term clinical follow-up (30.8 7.5 months). An incremental change in volume of the left atrial cavity was an independent predictor of new-onset atrial fibrillation or CHF hospitalization (Table 2) [37]. Patients who survived the 12-month period showed an overall increase in left atrial volume of 1.86 þ 4 .01 ml/m2. The patients’ group displaying an increased left atrial volume exhibited low left ventricular ejection fraction, large &
Table 2. New-onset atrial fibrillation or hospitalization with heart failure according to changes in LAVI after a primary percutaneous coronary intervention Decreased LAVI (%)
Increased LAVI (%)
P value
Hospitalization with heart failure
1.80
17.60
