Author + information
- Received February 18, 2016
- Revision received March 21, 2016
- Accepted March 31, 2016
- Published online February 6, 2017.
- Kenya Kusunose, MD, PhDa,
- Yuta Torii, RMSb,
- Hirotsugu Yamada, MD, PhDa,∗ (, )
- Susumu Nishio, RMSb,
- Yukina Hirata, RMS, PhDb,
- Hiromitsu Seno, MDa,
- Yoshihito Saijo, MDa,
- Takayuki Ise, MD, PhDa,
- Koji Yamaguchi, MD, PhDa,
- Takeshi Tobiume, MDa,
- Shusuke Yagi, MD, PhDa,
- Takeshi Soeki, MD, PhDa,
- Tetsuzo Wakatsuki, MD, PhDa and
- Masataka Sata, MD, PhDa
- aDepartment of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan
- bUltrasound Examination Center, Tokushima University Hospital, Tokushima, Japan
- ↵∗Address for correspondence:
Dr. Hirotsugu Yamada, Department of Cardiovascular Medicine, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima, Japan 770-8503.
Objectives This study sought to assess the time course of presumptive tachycardia-induced cardiomyopathy and the predictors of left ventricular (LV) functional recovery in such patients.
Background Tachycardia-induced cardiomyopathy is a potentially reversible cardiomyopathy with effective treatment of the tachyarrhythmia. However, cases without improvement of LV systolic function were found occasionally. The diagnosis of tachycardia-induced cardiomyopathy can be challenging, and the role of echocardiographic imaging in the prediction of LV functional recovery is limited.
Methods LV segmental longitudinal strains (LS) were evaluated by 2-dimensional speckle tracking in 71 consecutive patients (65 ± 16 years; 61% men) with tachyarrhythmia and reduced left ventricular ejection fraction (LVEF) without any other known cardiovascular disease, and 30 age and sex-matched control subjects. Relative apical LS ratio (RALSR) was defined using the equation: average apical LS / (average basal LS + average mid LS) as a marker of strain distribution.
Results Compared with control subjects, patients with tachyarrhythmia had significantly lower global LS. Improvement in LVEF within 6 months after treatment of index arrhythmia was observed in 41 patients, and LVEF did not improve in 30 patients. In univariate analysis, lower LVEF at baseline (hazard ratio: 0.59 per 1 SD; p = 0.04) and higher RALSR (hazard ratio: 11.2 per 1 SD; p < 0.001) were associated with no recovery in LVEF during follow-up. In a multivariate logistic regression model, the significant predictor of LV systolic functional recovery was RALSR (hazard ratio: 22.9 per 1 SD; p = 0.001). A RALSR of 0.61 was sensitive (71%) and specific (90%) in differentiating LV systolic functional recovery (area under the curve: 0.88).
Conclusions The RALSR was associated with LV systolic functional recovery. This information might be useful for clinical evaluation and follow-up in patients with reduced LVEF.
Long-standing tachycardia is a well-known cause of left ventricular (LV) dysfunction and heart failure. This type of LV dysfunction is called tachycardia-induced cardiomyopathy (TIC) (1). TIC is an acquired, potentially reversible form of cardiomyopathy characterized by atrial and/or ventricular myocardial dysfunction resulting from increased atrial and/or ventricular rate (2–5). The diagnosis is usually made after demonstrating recovery of LV function with treatment of arrhythmia in the absence of other identifiable etiologies (6). However, cases without improvement of LV systolic function were found occasionally in the clinical setting. The incidence of TIC is not well characterized, but it is estimated that approximately 50% of patients in tachyarrhythmia have impairment of LV systolic function (7). Some previous studies showed that risk factors for the development of TIC were older age and higher premature ventricular contraction (PVC) burden compared with control subjects (8). A better understanding of the mechanism and improved recognition of its presence can be clinically relevant to the prognosis of patients with tachyarrhythmia.
Quantitation of myocardial deformation is an emerging field of clinical cardiac imaging. In addition, recent clinical work using speckle tracking imaging shows that there are significant differences in regional strain in several cardiomyopathies, even in the absence of ischemia. Knowledge of the characteristic LV strain distribution pattern facilitates diagnosis for constrictive pericarditis, cardiac amyloidosis, hypertrophic cardiomyopathy, and hypertensive heart disease (9–13). Characteristic of strain distribution may help in the differential diagnosis of individual patients. In our previous study, longitudinal strain (LS) slightly increased from base to apex in control subjects. In contrast, decreased LS was more profound in the apex in animal models of rapid pacing-induced cardiomyopathy (14). Thus, this “reverse” distribution of LV strain may help to understand LV dysfunction in the presence of tachyarrhythmia.
The aim of this study was to investigate incidence, time course, and echocardiographic predictors of functional recovery in LV systolic function in a prospective and consecutive group of patients with reduced left ventricular ejection fraction (LVEF) and tachyarrhythmia.
We designed a prospective study to assess the LV functional recovery in patients with tachyarrhythmia. A total of 304 consecutive patients having supraventricular/ventricular tachyarrhythmia were referred to our echocardiographic examination center between January 2013 and February 2016. Reasons for referral included tachyarrhythmia (heart rate >100 beats/min) noted on resting 12-lead electrocardiogram, telemetry monitoring, or 24-h Holter monitor. Patients were excluded because of the following criteria: preserved LVEF (>50%; n = 160), incomplete echocardiographic follow-up (n = 55), coronary artery disease (≥70% stenosis of any major epicardial vessel; n = 18), hypertension (n = 12), diabetes mellitus (n = 4), hypertrophic cardiomyopathy (n = 3), moderate or severe valvular disease (n = 2), end-stage renal disease (n = 4), and stress-induced cardiomyopathy (n = 5). There were no patients with New York Heart Association functional class III or IV symptoms. After exclusions, 71 patients remained for final analysis who had LVEF ≤50% and who were diagnosed as presumptive TIC (Figure 1). Thirty age- and sex-matched control patients were selected from our healthy volunteer database based on a comprehensive history and physical examination. The Institutional Review Board of the Tokushima University Hospital approved the study protocol and written informed consent was obtained from all subjects.
A detailed medical history was obtained in all patients. Every patient had 12-lead electrocardiogram during his or her index clinical arrhythmia. Twenty-four-hour Holter monitoring was performed to evaluate the frequency of arrhythmia (arrhythmia burden: the ratio of total number of premature atrial/ventricular contractions to total heartbeat). Patients were classified into 3 groups according to the index arrhythmia: 1) atrial fibrillation; 2) paroxysmal supraventricular tachycardia including atrioventricular re-entry tachycardia and AV nodal re-entry tachycardia; and 3) monomorphic PVCs or nonsustained ventricular tachycardia. In patients undergoing initiation of medical antiarrhythmic therapy or cardiac catheter ablation, echocardiographic measurements were repeated within 6 months of index clinical arrhythmia. The primary endpoint was LV functional recovery during follow-up, defined as improvement of LVEF ≥15% or improvement of LVEF ≥10% to more than 50% after effective treatment of index clinical arrhythmia (6).
Standard echocardiographic assessment
Transthoracic echocardiography was performed by experienced sonographers/doctors using a commercially available ultrasound machine (iE33, Philips Healthcare, Amsterdam, the Netherlands; Vivid E9, GE Healthcare, Waukesha, Wisconsin; and SSA-770A, Toshiba Medical, Otawara, Japan). Measurements and recordings were obtained according to the American Society of Echocardiography recommendations (15). LV end-diastolic volume, LV end-systolic volume, left atrial volume, and LVEF were calculated by the biplane method of disks using 2-dimensional images and indexed to body surface area. The early diastolic (eʹ) mitral annular tissue velocity was also measured in the apical 4-chamber view with the sample volume positioned at the lateral mitral annulus. The systolic transtricuspid pressure gradient (PG) was calculated by the modified Bernoulli equation using maximal continuous-wave Doppler velocity of the tricuspid regurgitant (TR) jet. Tricuspid annular plane systolic excursion was measured as the distance of systolic movement of the junction between the tricuspid valve and the RV free wall using M-mode in accordance with current guidelines (16).
2-Dimensional strain echocardiography
Peak systolic LS measurements were obtained from gray-scale images recorded in the apical 4-chamber, 2-chamber, and long-axis views. The frame rate was maintained at a level >50 frame/s. LV strain was analyzed offline using speckle tracking software (EchoInsight, Epsilon Imaging, Ann Arbor, Michigan). Good image quality was defined as clear detection of the endocardial border throughout the cardiac cycle, and regions of interest at the apex and annulus were ensured. After manual definition of the LV endocardial border, the endocardium was automatically tracked throughout the cardiac cycle. The software algorithm automatically divided the LV apical view into 6 segments for speckle tracking throughout the cardiac cycle. Global longitudinal strain (GLS) was obtained by averaging all segmental strain values from the apical 4-chamber, 2-chamber, and long-axis views. Strain values for the 6 basal, 6 mid, and 6 apical segments of the LV were averaged to obtain regional LS values (basal, mid, and apical, respectively) (14,17). Relative apical longitudinal strain ratio (RALSR) was calculated by dividing the apical LS by the sum of the basal and mid-LS values (Figure 2) (11). These offline analyses were independently performed in a blinded manner by 2 observers who were not involved in the image acquisition and had no knowledge of examination dates and other echocardiographic or clinical data.
Data are presented as mean ± SD. Normality was assessed using the Kolmogorov-Smirnov test. One-way general linear model analysis of variance, followed by Dunnett T3 post hoc test analysis, was used to assess the difference between parameters in patients with improvement versus without improvement in EF. Logistic regression analysis was used to evaluate the associations between several potential variables and improvement in EF. Identified variables (p < 0.20 in the univariate model) were considered to enter in a stepwise manner into a multivariate logistic regression model. We checked for collinearity among predictors by using Pearson correlation coefficients, and no evidence had been found for collinearity problems in our model (variance inflation factor values <2). Receiver-operating characteristic curve analysis was used to identify parameters that were best to diagnose improvement in EF. The best cutoff value was based on the maximum Youden index. The method of DeLong was used to compare the C statistic (18). To assess the changes of LVEF before and after treatment of index arrhythmia, we applied a linear mixed effects model with unstructured covariance for random effects using standard statistical software (SPSS software 20.0; SPSS Inc., Chicago, Illinois). We used patient groups as factors, time after initial echocardiographic assessment as a covariate, and their first-degree interactions (time × groups) with the significance of the corresponding parameter estimates reported in the results. Reproducibility was expressed as the mean percentage error (absolute difference divided by the average of the 2 observations). Measurement was performed in 20 randomly selected subjects by 1 observer and then repeated on 2 separate days by 2 observers who were unaware of the measurements of the others and of the study time point. The intraobserver and interobserver variability of the LS was 7.4 ± 4.2% and 9.1 ± 5.3%.
Patient characteristics and treatment of tachyarrhythmia
Baseline characteristics of the study group are presented in Table 1. The study population consisted of 71 patients (65 ± 16 years; 61% men) with LVEF of 50% or less and diagnosed as presumptive TIC and 30 control subjects. Compared with control subjects, patients with tachyarrhythmia had significantly lower GLS. Presenting symptoms were palpitation in 30 patients (42%), syncope in 4 patients (6%), shortness of breath in 12 patients (17%), and no symptoms in 25 patients (35%). Atrial fibrillation was the most common underlying the index arrhythmia (n = 43; 61%), followed by paroxysmal supraventricular tachycardia (n = 15; 20%) and PVCs/ventricular tachycardia (n = 13; 10%). There was no association of symptoms/type of tachyarrhythmia with the primary endpoint in this cohort.
Effective treatment of index tachyarrhythmia was achieved in all patients with presumptive TIC with either antiarrhythmic drugs or catheter ablation. Twenty-seven patients underwent electrophysiological study and catheter ablation. Effective treatment of index tachyarrhythmia was achieved with drugs in 44 patients: bisoprolol in 16 patients, carvedilol in 10, amiodarone in 8, and verapamil in 10. Elimination of index tachyarrhythmia was achieved in 23 of 27 (85%) patients treated with radiofrequency ablation and 30 of 44 (68%) patients treated with antiarrhythmic drugs. Followed Holter recordings were available in 59 patients (83%). After the treatment of index tachyarrhythmia, averaged total heartbeats were decreased in both groups with and without improvement in LVEF (from 122,909 ± 13,999 to 102,418 ± 15,068 and from 129,256 ± 22,119 to 109,767 ± 14,012; both p < 0.001). Averaged arrhythmia burdens were also decreased in both groups (from 13.6 ± 6.9 to 1.5 ± 1.9 and from 17.5 ± 11.8 to 2.5 ± 2.9; both p < 0.001). There were no statistical differences of total heartbeats and arrhythmia burdens between groups with and without improvement in LVEF.
Prediction of improvement in EF
Improvement in LVEF within 6 months of treatment of index tachyarrhythmia was observed in 40 of 71 patients (64 ± 16 years; 58% men). LVEF did not improve in 31 of 71 patients (67 ± 14 years; 64% men). They remained unchanged at 6-month follow-up and were considered to be suffering from another cause of cardiomyopathy. Pre-onset echocardiographic data showed that LV function was preserved before the onset of LV dysfunction in both groups (n = 46). In patients with improved LVEF, the average LVEF improved from 39 ± 8% to 53 ± 12% after treatment of the index tachyarrhythmia. In patients without improvement in LVEF, average LVEF remained unchanged from 35 ± 10% to 36 ± 9% after treatment of the index ventricular arrhythmia (Figure 3). In patients with improvement in LVEF, GLS and RALSR increased from −10 ± 3% to −14 ± 3% and from 0.45 ± 0.10 to 0.59 ± 0.07 after treatment of the index tachyarrhythmia (both p < 0.001). In contrast, GLS and RALSR remained unchanged from −9 ± 3% to −10 ± 3% (p = 0.46) and from 0.69 ± 0.16 to 0.67 ± 0.12 (p = 0.68) in patients without improvement in LVEF (Figure 4). Patients without improvement in LVEF had significantly enlarged LV size, reduced LVEF, increased E/eʹ, and elevated TR-PG at baseline (all p < 0.05) (Table 1). In 2-dimensional speckle tracking echocardiography, patients without improvement in LVEF had significantly lower basal LS, lower mid-LS, and higher RALSR than the remainder (all p < 0.01).
To determine the predictors of recovery in LVEF, we performed univariate and multivariate analysis of association between baseline clinical and echocardiographic variables and recovery in LVEF during follow-up. In the univariate model, recovery in LVEF was correlated with LV size, LVEF, E/eʹ, TR-PG, basal LS, mid LS, and RALSR (Table 2). In the stepwise multivariate logistic regression model, recovery in LVEF was correlated with TR-PG (hazard ratio: 5.3; 95% confidence interval: 1.67 to 16.6; p = 0.005) and RALSR (hazard ratio: 22.9; 95% confidence interval: 3.40 to 153.76; p = 0.001) (Table 2). Results of the receiver operating characteristic curve analysis used to identify the optimal cutoff point for predicting the improvement in LVEF during follow-up are shown in Figure 5. A RALSR of 0.61 was sensitive (71%) and specific (90%) in predicting LV systolic functional recovery. This RALSR had the highest area under the curve (0.88; p < 0.001) among echocardiographic variables. In a subgroup with successful catheter ablation (n = 23), a RALSR of 0.58 was also sensitive (93%) and specific (75%) in predicting LV systolic functional recovery with the high area under the curve (0.89; p < 0.001) (Online Table 1).
Our study sought to determine the prevalence and predictors of improvement in LVEF in patients with tachyarrhythmia and reduced LVEF using echocardiography including speckle tracking imaging. Our study brings several new insights into the understanding of improvement in LVEF in patients with tachyarrhythmia: 1) no recovery in LVEF occurred in about 42% of patients with presumptive TIC; 2) LV size, LVEF, E/eʹ, and TR-PG at baseline predicted improvement of LVEF; and 3) strain distribution (e.g., RALSR) was the most powerful independent predictor of improvement of LVEF during follow-up. The decrease of strain was more profound in the apex in patients with improvement in LVEF. Interestingly, the relatively preserved apical strain was shown in patients without improvement in LVEF. This information might be useful for clinical evaluation and follow-up in patients with reduced LVEF before the treatment of index arrhythmia (e.g., catheter ablation).
Predictors of recovery in LVEF
The incidence of TIC has been described as ranging from 10% to 50% in patients with atrial/ventricular tachyarrhythmia (4,19,20). In PVCs, risk factors for the development of TIC were reported to be older age and higher PVC burden compared with control subjects (8). In atrial tachycardia, younger patients, males, those with slower heart rate, and incessant tachyarrhythmia are more likely to have reduced LVEF in tachyarrhythmia (4). In our cohort, there was no association of arrhythmia type with incidence of LV functional recovery. There are some controversial findings in the literature in regards to the recovery of LVEF. Classically, the diagnosis of TIC is made after demonstrating recovery of LV function with treatment of arrhythmia. Despite strict exclusion criteria of other cardiomyopathy causes, LVEF recovery occurred in only 55% of patients with presumptive TIC in our cohort. This finding emphasized the importance of follow-up echocardiography, because some cases do not recover LVEF in patients with presumptive TIC.
Our study also demonstrated the prognostic power of LV size, LVEF, E/eʹ, and TR-PG at baseline. The results of this study are consistent with the previous basic work demonstrating the mechanism of TIC. In animal models of pacing-induced HF, sustained atrial or ventricular pacing produced severe biventricular systolic dysfunction (21–23). This is characterized by increased ventricular filling pressures, decreased cardiac output, and increased systemic vascular resistance. In the no functional recovery group, LV systolic dysfunction (e.g., LV size and LVEF) and diastolic function (e.g., E/eʹ and TR-PG) frequently occurred compared with the recovery group. There were several pathophysiological mechanisms in TIC, such as diastolic interval change, myocardial blood flow, neurohormonal changes, and oxidative stress (6). Traditionally, it has been believed that functional recovery usually occurred in TIC. Thus, our data suggest that there is some occult LV dysfunction in tachyarrhythmia in the clinical setting.
Mechanics of TIC
The clinical utility of advanced echocardiographic imaging, such as 2-dimensional speckle tracking, has been supported by numerous studies. In recent years, a number of literature citations showed that the assessment of strain distribution has emerged as an aid in the diagnosis of several causes of cardiomyopathy with nonischemic etiology (9–13). In an animal study, the decrease of LS was more profound in the apex in rapid pacing animal models (14). In our cohort, the patients with recovery in LVEF had a “reverse” distribution similar to the previous works. A possible explanation could be that basal and mid-ventricular levels were protected from stress increases and subsequent remodeling by the mitral annulus and papillary muscles in patients with tachyarrhythmia.
Interestingly, apical strain was relatively preserved in patients without recovery in LVEF. Previous papers described that LS in the basal and mid-segments of the LV is more severely impaired compared with the strain values in the apical segments in patient with infiltrative cardiomyopathies and with a systemic disease (e.g., amyloidosis) (11,24). A potential pathophysiological mechanism of apical sparing may be heterogeneous myocardial deposition. In addition, 1 previous study showed that the myocardial scar burden was associated with impaired recovery in LVEF in patients with PVCs or ventricular tachycardia (25). Apical sparing may be a marker of occult myocardial impairment in patients with tachyarrhythmia.
To the best of our knowledge, this is the first report of strain distribution and may help differentiate that type of cardiomyopathy from other possible causes of decreased systolic function. RALSR is a simple and reproducible assessment for strain distribution. Subjects at higher risk, such as those with higher RALSR, are known to have an abnormal response in LVEF during follow-up. RALSR may prove to be a noninvasive surrogate to predict LV recovery in patients with tachyarrhythmia. Although this study suggests an association between strain distribution and LV functional recovery, the results should be tested on a large cohort of patients with tachyarrhythmia using other cardiovascular imaging modalities (e.g., cardiac magnetic resonance [CMR]) to detect the occult cardiomyopathy.
Because of the strict exclusion criteria including complete follow-up and a small single-center study, the sample size was small with relatively few endpoints. We could not enter some clinical variables (e.g., age, sex, heart rate) into the model because of the relatively small number of outcomes (31 events), which poses a potential risk of model overfit. Therefore, we were unable to completely adjust our model. The present study should be considered as a proof of concept, and we believe larger multicenter studies are warranted. It was hard to determine the duration of tachyarrhythmia in most patients. We could not determine the temporal relationship between duration of tachyarrhythmia and improvement in LVEF. We did not have myocardial damage data on other cardiovascular imaging modalities (e.g., delayed enhanced imaging of CMR) and were unable to determine detailed characteristics in patients without functional recovery. Despite the exclusion of known cardiovascular diseases, we may not have been able to avoid the potential effect on myocardial mechanics by the other unknown etiologies. Some investigators showed that patients without functional recovery had myocardial scar by late gadolinium enhancement. Although this study suggests an association between strain distribution and LV functional recovery, this hypothesis should be tested on a large cohort of patients with tachyarrhythmia (late gadolinium enhancement [LGE]-CMR imaging) (26). In our cohort, LGE-CMR imaging was performed in 4 of 30 patients with recovery in LVEF and 10 of 41 patients without recovery in LVEF. One of 4 patients (25%) had LGE in patients with recovery in LVEF and 7 of 10 patients (70%) had LGE in patients without recovery in LVEF. Our results suggested that if patients with presumptive TIC had high RALSR, we may recommend LGE-CMR to check the occult cardiomyopathy.
Assessment of RALSR can be considered a useful tool in patients with tachyarrhythmia and reduced LVEF. This study highlights the use of strain distribution in patients with a nonischemic etiology. This knowledge may be useful for clinical evaluation and follow-up of patients with reduced LVEF and tachyarrhythmia (presumptive TIC). We might consider that patients without functional recovery had occult myocardial damage caused by a nonischemic etiology. Further studies are needed to assess whether strain can be used to assess the prognostic value in tachyarrhythmia in long-term follow-up.
COMPETENCY IN MEDICAL KNOWLEDGE: The relative apical longitudinal strain ratio obtained by 2-dimensional speckle tracking echocardiography was a predictor of left ventricular systolic functional recovery in patients with reduced LVEF and tachyarrhythmia. This information might be useful for clinical evaluation and follow-up in patients with reduced LVEF before the treatment of index arrhythmia.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: Strain distribution should be carefully assessed in patients with reduced LVEF and tachyarrhythmia. Our results suggest the importance of follow-up echocardiography, because some patients with presumptive tachycardia-induced cardiomyopathy do not recover LVEF.
TRANSLATIONAL OUTLOOK: Although this study suggests an association between strain distribution and left ventricular functional recovery, this hypothesis should be tested on a large cohort of patients with tachyarrhythmia.
The authors thank Kathryn Brock, BA, for her work editing the manuscript.
For a supplemental table, please see the online version of this article.
This work was partially supported by JSPS Kakenhi (grant 15K19381 to Dr. Kusunose; and 24659392, 22390159, 25670390, and 25293184 to Dr. Sata), Japan Heart Foundation Research (Dr. Kusunose), and MEXT KAKENHI (grant 21117007 to Dr. Sata). All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- cardiac magnetic resonance
- ejection fraction
- global longitudinal strain
- late gadolinium enhancement
- longitudinal strain
- left ventricular
- premature ventricular contraction
- relative apical longitudinal strain ratio
- tachycardia-induced cardiomyopathy
- tricuspid regurgitant pressure gradient
- Received February 18, 2016.
- Revision received March 21, 2016.
- Accepted March 31, 2016.
- American College of Cardiology Foundation
- Yarlagadda R.K.,
- Iwai S.,
- Stein K.M.,
- et al.
- Medi C.,
- Kalman J.M.,
- Haqqani H.,
- et al.
- Shinbane J.S.,
- Wood M.A.,
- Jensen D.N.,
- Ellenbogen K.A.,
- Fitzpatrick A.P.,
- Scheinman M.M.
- Kusunose K.,
- Dahiya A.,
- Popovic Z.B.,
- et al.
- Phelan D.,
- Collier P.,
- Thavendiranathan P.,
- et al.
- Foell D.,
- Jung B.,
- Germann E.,
- Staehle F.,
- Bode C.,
- Markl M.
- Chang S.A.,
- Kim H.K.,
- Kim D.H.,
- et al.
- Kusunose K.,
- Zhang Y.,
- Mazgalev T.N.,
- Thomas J.D.,
- Popovic Z.B.
- Lang R.M.,
- Badano L.P.,
- Mor-Avi V.,
- et al.
- Rudski L.G.,
- Lai W.W.,
- Afilalo J.,
- et al.
- Moe G.W.,
- Armstrong P.
- McMahon W.S.,
- Mukherjee R.,
- Gillette P.C.,
- Crawford F.A.,
- Spinale F.G.
- Lagies R.,
- Beck B.B.,
- Hoppe B.,
- Sreeram N.,
- ten Cate F.E.A.U.