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Echocardiographic quantification of systolic function during atrial fibrillation: probing the ‘ten heart cycles’ rule Flemming Javier Olsen*,1, Peter Godsk Jørgensen1,2, Maria Dons1, Jesper Hastrup Svendsen2,3, Lars Køber2,3, Jan Skov Jensen1,2 & Tor Biering-Sørensen1,4 It is often difficult to provide an exact echocardiographic measure of left ventricular systolic function in patients with atrial fibrillation, partly because of the varying cycle length affecting pre and afterload and partly because of the increased heart rate often accompanying this arrhythmia. We sought to elucidate two points: whether it would be possible to correct for the cyclic variance in systolic output, and if global longitudinal strain is preferable to the left ventricular ejection fraction at evaluating systolic function during atrial fibrillation. First draft submitted: 16 July 2015; Accepted for publication: 9 November 2015; Published online: 26 February 2016 Patients presenting with atrial fibrillation (AF) rhythm exhibit beat-to-beat fluctuations in loading conditions and mechanics [1] . This often makes it difficult to adequately quantify systolic function as the left ventricular ejection fraction (LVEF) carries great load dependency [2] . In order to circumvent this issue, it is generally recommended to average the systolic assessment over several (i.e., ten) cardiac cycles [3] . We have, however, not been able to find any evidence to support this approach for LVEF evaluation. Furtehermore, since this is quite a time consuming approach, it does not seem as a feasible undertaking in daily clinical practice. Another way of estimating systolic function is, therefore, clinically warranted. Based on a case experience we tried to explore the options available for evaluating systolic performance in patients with AF in search of an expedient solution.


• atrial fibrillation • echocardiography • global longitudinal strain • myocardial deformation • systolic function

Case We report a case of an elderly woman (age: 72) who presented with new-onset asymptomatic AF when she came in for an echocardiogram as part of a research study. The arrhythmia was confirmed with a 12-lead ECG (Figure 1) . Her baseline characteristics are outlined in Box 1. She underwent a comprehensive echocardiographic investigation and converted spontaneously to sinus rhythm during the exam, allowing for image acquisition in both rhythm states. GE Vivid EchoPAC BT12 was utilized for echocardiographic analysis. LVEF by Simpson’s biplane and global longitudinal strain (GLS) by semiautomated speckle tracking were compared between the two rhythms. Measurements during AF were performed over ten cardiac cycles compared with six cardiac cycles in sinus rhythm. RR intervals were measured using a manual caliper on the images’ respective Department of Cardiology, Herlev & Gentofte Hospital, University of Copenhagen, Denmark, Niels Andersens Vej 65, 2900 Hellerup, Denmark 2 Institute of Clinical Medicine, Faculty of Health & Medical Sciences, University of Copenhagen, Denmark 3 Department of Cardiology, Rigshospitalet, University of Copenhagen, Denmark 4 Department of Medicine, Cardiovascular Medicine Division, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA *Author for correspondence: Tel.: +45 31 44 12 29; [email protected] 1

10.2217/fca.15.77 © 2016 Future Medicine Ltd

Future Cardiol. (2016) 12(2), 159–165

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ISSN 1479-6678


Case Report  Olsen, Jørgensen, Dons et al.














Figure 1. Patient’s ECG. 12-lead ECG taken to confirm atrial fibrillation rhythm.

electrocardiographic traces. A time interval of 8 minutes passed between the two rhythms’ measurements. Measurements per cardiac cycle are presented in Table 1. During AF the patient had an LVEFavg = 44.3% (SD = 4.6%) and GLSavg = -15.4% (SD=1.9%) as opposed to sinus rhythm presenting with an LVEFavg = 56.0% (SD=2.2%) and GLSavg = -21.7% (SD = 0.8%). Both measures emphasize a marked difference between the two rhythm states, with apparently depressed systolic function during AF (visualized in Figure 2A & B). As an alternate approach we sought to correct for the heart rate variability by the RR interval. We created linear regression models with LVEF and GLS plotted against the RR interval in both rhythms (GLS plots: Figure 3A & Figure 3B ). The following slopes were derived: LVEFsinus = 138.1%/s, LVEFAF = 16.5%/s, GLS sinus = 17.2%/s, GLS AF = 15.2%/s. We further explored this by performing paired samples t-tests between GLSsinus /RR sinus and GLSAF/RR AF and between LVEFsinus /RR sinus and LVEFAF/RR AF. We observed that LVEF/RR in sinus rhythm compared with AF was significantly different (mean difference = 20.2%/s; SD = 17.9%/s; p = 0.039), whereas GLS/RR in sinus rhythm did not differ significantly from AF rhythm (mean difference = 4.0%/s;


Future Cardiol. (2016) 12(2)

SD = 5.3%/s; p = 0.12). Bland–Altman plots of these variables were made and revealed the measurements of LVEF/RR to be markedly more dispersed than GLS/RR measurements (Figure 4A–D) . We also examined GLS and LVEF indexed to the RR interval of the preceding cardiac cycle, however, this did not yield any significant correlation in any of the measures between the two rhythm states. Discussion Our case-based findings highlight some important clinical aspects. First of all, that averaging several cardiac cycles during AF may give the impression of an apparently reduced systolic function, not actually reflecting the full systolic capabilities. Even though the tachycardia could confer a slight negative inotropic effect [5] , this finding likely reflects a methodological underestimation problem caused by the relatively high heart rate [2] . Second, we demonstrated that GLS indexed by the RR interval correlates well between sinus rhythm and AF, which was not the case for LVEF. This may reflect that GLS is less loading dependent [6] . The present presentation is meant as a hypo­ thesis generating observation as we are clearly limited by this being a single-case experience. The GLS/RR may though offer a way of quantifying systolic function in this patient group, which

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Echocardiographic quantification of systolic function during AF: probing the ‘ten heart cycles’ rule 

Case Report

Box 1. Baseline characteristics. Medical history ●● Age: 72 ●● Nonsmoker ●● Hypertension ●● Previous stroke ●● Previous transient ischemic attack Stroke risk score [4] ●● CHADS2 = 3 ●● CHA2DS2-VASc = 5 Medication ●● Amlodipin 10 mg × 1 daily ●● Simvastatin 20 mg × 1 daily ●● Clopidogrel 75 mg × 1 daily Physical ●● BMI = 20.9 ●● NYHA class = 1 Structural heart disease on transthoracic echocardiogram ●● Mild mitral regurgitation ●● Mild aortic regurgitation ●● Mild tricuspid regurgitation

●● Mild pulmonic regurgitation CHADS2: Congestive heart failure (1 point), hypertension (1 point), age ≥75 (1 point), diabetes (1 point), stroke (2 points). CHA2DS2VASc: Congestive heart failure (1 point), hypertension (1 point), age ≥75 (2 points), diabetes (1 point), stroke (2 points), vascular disease (1 point), age: 65–74 (1 point), sex (female, 1 point in the presence of other risk factors). NYHA: New York Heart Association.

is much needed both in clinical and research aspects. As mentioned earlier, averaging systolic measurements over several heart cycles can be tiresome and thus unfeasible. This may leave clinicians to bypass this method in favor of an eyeball evaluation, thereby running a risk of overlooking subtle systolic impairment. Furthermore, many studies tend to omit or exclude AF patients as the measurements from this particular patient

group may modify the findings, creating ambiguity as to the effect of an intervention. Although this may seem fair in respects to clarifying the role of a specific intervention, it entails a problem as to whether a given medical intervention would also benefit AF patients. This is particularly true in patients with overt heart failure, where a substantial proportion of patients may suffer from AF.

Table 1. Systolic measurements per cycle. Case

Sinus rhythm

Atrial fibrillation rhythm


LVEF (%)

RR for LVEF (s)

LVEF/RR (%/s)

GLS (%)

RR for GLS (s)

GLS/RR (%/s)

LVEF (%) RR for LVEF (s)

LVEF/RR (%/s)

GLS (%)

RR for GLS (s)

GLS/RR (%/s)

1 2 3 4 5 6 7 8 9 10

59 55 54 55 54 59        

0.77 0.77 0.75 0.77 0.76 0.77        

76.2 71.5 72.5 71.5 70.7 76.7        

-22.4 -22.3 -22.6 -20.6 -20.8 -21.5        

0.79 0.78 0.76 0.77 0.77 0.77        

-28.5 -28.6 -29.8 -26.8 -27.1 -27.8        

50 38 43 44 42 41 49 44 53 39

125.8 92.8 91.3 106.7 100.8 97.7 121.7 73.0 93.6 83.9

-17.1 -14.3 -14.6 -14.1 -15.9 -12.9 -16.9 -13.6 -19.8 -15.3

0.45 0.43 0.50 0.46 0.47 0.42 0.40 0.52 0.55 0.49

-38.2 -33.2 -29.3 -30.9 -33.7 -30.9 -41.7 -26.2 -36.2 -31.5

0.40 0.41 0.47 0.41 0.42 0.42 0.40 0.60 0.57 0.47

GLS: Global longitudinal strain; LVEF: Left ventricular ejection fraction; RR: Time interval between peak R-waves.

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Case Report  Olsen, Jørgensen, Dons et al.

Maks systoilsk strain ANT_SEP


-19 SEPT



-16 -22

-25 -20


-20.0 %


-24 -25




-22 -24




-25 POST 08/01/2015 – 19:47:55 GLPS_LAX GLPS_A4C GLPS_A2C GLPS_Arg

-22.0 % AVC_AUTO -21.4 % HR_ApLAX -22.0 % FR_min -22.4 %

Maks systoilsk strain ANT_SEP

298 msec 74 apm 59 fps


-15 SEPT



-13 -15

5 -21


-20.0 %


-21 -10 -7 INF





-15 LAT

7 POST 08/01/2015 – 19:46:14 GLPS_LAX GLPS_A4C GLPS_A2C GLPS_Arg


-17.1 % AVC_AUTO -14.8 % HR_ApLAX -11.7 % FR_min -14.1 %

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267 msec 123 apm 67 fps

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Echocardiographic quantification of systolic function during AF: probing the ‘ten heart cycles’ rule 


Figure 2. Strain deformation values in both rhythms (see facing page). Automated function imaging performed during the echocardiographic examination to illustrate the myocardial systolic function in sinus rhythm (A) and during atrial fibrillation (B). (A) Bulls eye plot reveals completely preserved systolic function. (B) Bulls eye plot illustrates substantially impaired systolic function, particularly in the basal segments of the left ventricle.

Speckle tracking is an emerging technique in deformation analysis, and studies have shown that strain measurements may be superior to LVEF in several clinical applications. Specifically it has shown to be a quite sensitive marker for early myocardial systolic dysfunction [7] , and has already been incorporated in guidelines for certain clinical conditions [8] . Thus, introducing GLS in the evaluation of these patients may also offer additional insight into preclinical cardiac ailment. However, some general limitations do exist when applying both LVEF and GLS, which may mandate a search for other systolic parameters of potential use. Patients with AF often present with

Global longitudinal strain (%)


increased heart rate, which may exceed the frame rate obtained by 2D grayscale imaging. This could potentially mean that one does not have enough image frames to capture the precise left ventricular volumes needed to calculate the LVEF accurately by the Simpson’s biplane method. This matter, however, not only influences the Simpson’s biplane but also speckles tracking imaging for strain deformation analysis. Strain deformation values were though first introduced as a derivative of tissue Doppler images, and this modality may achieve a frame rate of 150–200 [9] . Such high temporal resolution may provide an even stronger solution to the problem of ascertaining left ventricular

f(x) = 17.2x + 8.4

25 20 15 10 5 0 0.755








RR interval (s)

Global longitudinal strain (%)


f(x) = 15.2x + 8.3

25 20 15 10 5 0 0.35






RR interval (s)

Figure 3. Linear regressions of global longitudinal strain by time interval between peak R-waves. Global longitudinal strain plotted against the RR interval in sinus rhythm (A) and atrial fibrillation (B) to visualize its dependency on the RR interval and the close correlation between the two rhythms. RR: Time interval between peak R-waves.

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Case Report  Olsen, Jørgensen, Dons et al.

Left ventricular ejection fraction 30.00







Global longitudinal strain 15.00








0.00 15.00








Average of measurements





Average of measurements

Global longitudinal strain/RR

Left ventricular ejection fraction/RR




45.00 Difference


25.00 0.00



-25.00 -45.00



-75.00 26.00


30.00 32.00 34.00 Average of measurements




80.00 85.00 90.00 95.00 Average of measurements


Figure 4. Bland–Altman plots of measures’ agreement between sinus rhythm and atrial fibrillation. Values in (A) and (B) are presented as %, whereas values in (C) and (D) are presented as %/s. Solid lines represent mean value, and dotted lines represent 95% CI. (C) and (D) illustrate the values of global longitudinal strain/RR to show better agreement than left ventricular ejection fraction/RR. RR: Time interval between peak R-waves.

systolic performance and detection of early signs of myocardial impairment during AF. Studies are needed to elucidate the role of GLS/RR compared with LVEF/RR during AF, and whether tissue Doppler imaging derived strain measurements may be even more sturdy markers of systolic performance in these patients. Conclusion & future perspective The fluctuating estimates of systolic function in patients with AF may be counteracted by indexing the assessment with the RR interval.


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GLS may offer more credible insight into patients’ systolic performance than LVEF when indexed with the RR interval; however, more extensive studies are needed to validate this hypothesis. Disclaimer The patient was included as part of the LOOP study ( NCT02036450). This study was approved by a regional scientific ethics committee (H-42013-025), and informed consent was obtained from all participants.

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Echocardiographic quantification of systolic function during AF: probing the ‘ten heart cycles’ rule  Financial & competing interests disclosure The study was supported by the Innovation Fund Denmark (grant no.: 13-135225) and FJ Olsen was financed with a scholarship grant from the P Carl Petersen Foundation during preparation of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.


No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.


uantifying systolic function in patients with atrial fibrillation is challenging as they experience beat-to-beat variations Q in loading conditions.


urrently, it is recommended to average the left ventricular ejection fraction over several cardiac cycles; however, this C is time consuming and tiresome.


Global longitudinal strain has emerged as a new way of evaluating systolic function in various patient groups.

Conclusion & future perspective ●●

ur findings suggest that global longitudinal strain indexed to the RR interval (global longitudinal strain/RR) may be O valuable for the quantification of systolic function in atrial fibrillation patients. This measure should be investigated in a larger cohort.

References 1

Gosselink AT, Blanksma PK, Crijns HJ et al. Left ventricular beat-to-beat performance in atrial fibrillation: contribution of Frank–Starling mechanism after short rather than long RR intervals. J. Am. Coll. Cardiol. 26(6), 1516–1521 (1995).


Marwick TH. Methods used for the assessment of LV systolic function: common currency or tower of Babel? Heart 99(15), 1078–1086 (2013).


Wang C-L, Ho W-J, Luqman N, Hsu L-A, Kuo C-T. Biplane assessment of left ventricular function during atrial fibrillation at beats with equal subsequent cycles. Int. J. Cardiol. 113(1), 54–60 (2006).

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Mason PK, Lake DE, DiMarco JP et al. Impact of the CHA 2DS2-VASc score on anticoagulation recommendations for atrial fibrillation. Am. J. Med. 125(6), 603.e1–603.e6 (2012).


Herbert WH. Cardiac output and the varying R-R interval of atrial fibrillation. J. Electrocardiol. 6(2), 131–135 (1973).


Shah AM, Solomon SD. Myocardial deformation imaging: current status and future directions. Circulation 125(2), e244–e248 (2012).


Biering-Sørensen T, Hoffmann S, Mogelvang R et al. Myocardial strain analysis by 2-dimensional speckle tracking echocardiography improves diagnostics of

coronary artery stenosis in stable angina pectoris. Circ. Cardiovasc. Imaging 7(1), 58–65 (2014). 8

Authors/Task Force members, Elliott PM, Anastasakis A et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur. Heart J. 35(39), 2733–2779 (2014).


Abraham TP, Dimaano VL, Liang H-Y. Role of tissue Doppler and strain echocardiography in current clinical practice. Circulation 116(22), 2597–2609 (2007).


Echocardiographic quantification of systolic function during atrial fibrillation: probing the 'ten heart cycles' rule.

It is often difficult to provide an exact echocardiographic measure of left ventricular systolic function in patients with atrial fibrillation, partly...
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