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European Journal of Echocardiography Advance Access published online on September 18, 2008
European Journal of Echocardiography, doi:10.1093/ejechocard/jen239
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Impaired right ventricular systolic function demonstrated by reduced atrioventricular plane displacement in adults with Marfan syndrome

Anatoli Kiotsekoglou1, George R. Sutherland1, James C. Moggridge1, Venedictos Kapetanakis1, Abhay Bajpai1, Nicholas Bunce1, Michael J. Mullen2, George Louridas3, Dariush K. Nassiri1, John Camm1 and Anne H. Child1,*

1 Department of Cardiac and Vascular Sciences, St George’s, University of London, Cranmer Terrace, London SW17 0RE, UK
2 Royal Brompton and Harefield Hospital NHS Trust, Sydney Street, London SW3 6NP, UK
3 Department of Cardiology, AHEPA Hospital, Aristotle University of Thessaloniki, First Kiriakidi Street, Thessaloniki 546 36, Greece

Received 27 May 2008; accepted after revision 25 August 2008.

* Corresponding author. Tel: +44 208 7255248, fax: +44 208 7252653, E-mail address: achild{at}sgul.ac.uk


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Funding
 References
 
Aims: The right ventricle (RV) ejects the same volume of blood at the same rate as the left ventricle (LV). Mild LV dysfunction has been demonstrated in Marfan syndrome (MFS). However, little attention has been paid to the functioning of the RV. The aim of this study was to assess RV function in unoperated adult MFS patients.

Methods and results: In 66 unoperated (15–58 years) MFS patients and 61 controls, rate of pressure rise (dp/dt) in RV, and tricuspid annular motion (TAM) were studied using conventional echocardiography and tissue Doppler imaging (TDI). When compared with controls, MFS patients showed impaired RV systolic function as expressed by a reduced dp/dt, TAM obtained by M-mode echocardiography, and peak TDI systolic velocities at the basal lateral wall (745.36 ± 37.85 vs. 1103.30 ± 27.30 mmHg, P < 0.001; 2.2 ± 0.05 vs. 2.5 ± 0.05 cm, P < 0.001; and 0.13 ± 0.002 vs. 0.16 ± 0.002 m/s, P < 0.001, respectively).

Conclusion: This study demonstrated a primary impairment of RV systolic function in MFS. This is the first study to report RV dysfunction in MFS. Such data could prove valuable during the peri-operative and long-term medical management of MFS patients.

Keywords: Marfan syndrome; Right ventricular function; Systolic long-axis function; Tissue Doppler imaging


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Funding
 References
 
Marfan syndrome (MFS) is an inherited disorder of connective tissue characterized by ocular, musculoskeletal, and cardiovascular manifestations and caused by mutations in the fibrillin-1 (FBN1) gene that encodes the protein fibrillin-1.1 In 1991, the discovery of the FBN1 gene by an international consortium triggered off a sequence of exciting developments in the MFS research field. New insights regarding the protein fibrillin-1 have revealed its role not only as an important component of elastic fibres but also as a regulator of transforming growth factor-β (TGF-β) bioactivity in the extracellular matrix.2 Recently conducted experimental studies provide evidence that fibrillin-1 interacts with integrins and affects the cytokine TGF-β, which can influence matrix deposition, cellular proliferation, and cell death within the cardiovascular system.3 Therefore, causative mutations in the FBN1 gene may result in myocardial dysfunction.

Aortic complications have long been recognized as the main cause of premature death from MFS and have been studied extensively. Previous studies by Chatrath et al.4 and Meijboom et al.5 demonstrated left ventricle (LV) enlargement with normal LV systolic function in 19% and 7% of their MFS study groups, respectively. Moreover, a recent study by De Backer et al.6 demonstrated mild abnormalities in LV systolic and diastolic functions in patients with MFS. However, very little attention has been paid to the right ventricle (RV). It is presumed that the RV functions normally, and therefore less time is spent in assessing its performance compared with the aorta and LV.

Precise assessment of RV function is difficult due to the crescent shape of the ventricle and also to its complex morphology. In clinical practice, a useful way to estimate the RV function is to observe the tricuspid annular motion (TAM).7 When compared with both nuclear and magnetic resonance imaging, TAM was found to correlate extremely well with the RV ejection fraction (EF).8,9 To date, no study has been performed measuring TAM to evaluate RV function in MFS. Since the RV ejects the same volume of blood at the same rate as the LV, we sought to ascertain any abnormalities of RV systolic function in unoperated patients with MFS without significant valvular disease, using two dimensional, two dimensional-targeted M-mode, Doppler and colour tissue Doppler echocardiography.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Funding
 References
 
Seventy-one consecutive Caucasian patients who conformed to the internationally accepted Ghent criteria for MFS10 were enrolled in this echocardiographic study conducted at St George’s, University of London in collaboration with St George’s Hospital NHS Trust. Patients were recruited from the MFS clinics at St George’s, Royal Brompton and Harefield Hospitals. In each case, the clinical diagnosis was confirmed by two experienced observers (A.K. and A.H.C.). The main exclusion criteria were (i) age <15 or >60 years, (ii) aortic dissection or previous cardiac surgery, (iii) valvular disease more than mild in severity, (iv) persistent arrhythmias, (v) systemic and/or pulmonary hypertension, and (vi) other significant clinical disorders known to affect the myocardial function, such as coronary heart disease, diabetes mellitus, renal impairment, anaemia, thyroid, or liver disorders. After the application of these criteria, 5 of the 71 patients had to be excluded, giving a final study population of 66 MFS patients.

At baseline, 22 (33%) of the 66 patients were on treatment with β-blockers specifically prescribed for the management of MFS. Discontinuation of β-blockers for these patients was considered inappropriate for ethical reasons. Following clinical and echocardiographic examination to confirm the diagnosis of MFS, according to the Ghent criteria, the majority of the remaining patients not already on β-blocker therapy were referred to their managing physicians for appropriate treatment. Several patients under our direct supervision despite being fully informed about the risks have chosen to remain untreated for various reasons such as concerns over fatigue, religious issues, and, for male patients, impotence. Twenty-nine out of 66 patients already had a known causative FBN1 mutation identified through our research programme to confirm the clinical diagnosis.11 For the remaining subjects, DNA samples have been included in an ongoing analysis programme.

The control group consisted of 61 age, sex, race, height, weight, and body surface area (BSA) matched normal volunteers, selected from the general population and genetically unrelated family members of our patients.

All subjects underwent complete physical, electrocardiographic, and echocardiographic examination. Ethical approval was obtained from St George’s Hospital, NHS Trust Ethical Committee, and all participants provided written informed consent.

Echocardiography
M-mode, two-dimensional, colour Doppler, and colour tissue Doppler images were obtained through optimal parasternal, apical, and sub-xiphoid views using the Vivid 7 Vingmed General Electric ultrasound scanner (GE Vingmed Ultrasound, Horten, Norway) equipped with a 4S-MHz probe. Three consecutive cardiac cycles were recorded for each view, with breath held at end expiration. An ECG was recorded simultaneously at a sweep speed of 100 mm/s. Colour Doppler images were acquired at high frame rates of 180 ± 15, using narrow image sectors. All measurements were performed offline using Echopac 6.1, GE workstation.

Assessment of right ventricle thickness, size, and right ventricle/left ventricle ratio
The quantification of RV thickness and size complied with the ASE guidelines.7

Right ventricle free wall thickness was assessed from the sub-xiphoid view at the end-diastole at the level of the tricuspid valve chordae tendinae using two-dimensional imaging. The assessment of RV size was performed in a true non-foreshortened apical four-chamber view. Right ventricle diameters were measured at the basal and mid-cavity levels at the end-diastole. The RV size was also assessed from the short-axis view at mid-level to avoid false-positive dilatation. To calculate the RV/LV ratio, LV diameters were also measured at the basal level in the apical four-chamber view at the end-diastole. Right ventricle and LV diameters were measured in the transverse plane at their widest points between the inner surface of the free wall and the surface of interventricular septum. The diameter measurements were subsequently indexed for BSA.7 Pulmonary artery (PA) size, pressures, inferior vena cava (IVC) size, and inspiratory response were calculated in accordance with ASE recommendations for chamber quantification. Pulmonary artery and IVC diameters were also indexed for BSA.7

Assessment of right ventricle systolic function
Tricuspid annular motion was recorded using M-mode and tissue Doppler imaging (TDI) to assess the RV function. Tricuspid and pulmonary regurgitant jets were also recorded using colour Doppler technique.

Tricuspid regurgitant jet was recorded in the apical four-chamber view in order to evaluate the rate of pressure rise (dp/dt) in the RV (Figure 1A).12


Figure 1
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  		Figure 1 (A) Calculation of dp/dt from continuous wave Doppler recording over tricuspid regurgitant flow. (B) Two-dimensionally directed M-mode recording of the lateral tricuspid annular motion. (C) Tricuspid annular velocities obtained using tissue Doppler imaging.

 
Tricuspid annular motion was obtained by placing an M-mode sounding beam in the long-axis across the lateral tricuspid annular region (Figure 1B). Anatomical M-mode was used to overcome limitations with regard to parallel alignment of the M-mode beam to the RV free lateral wall. Colour tissue Doppler M-mode was used as an additional method to assess the amplitude of TAM, as this technique ensures high spatial and temporal resolutions. Measurements were performed 60 ms after the beginning of QRS to the peak displacement of the tricuspid annulus towards the apex in systole.13

For the acquisition of tissue Doppler velocities of the tricuspid annulus, data were collected in accordance with the recommendations for the quantification of Doppler echocardiography.14 Peak systolic velocity was measured avoiding the initial peak observed during isovolumic contraction time (Figure 1C).

Assessment of left ventricle systolic function
Left ventricle function was also assessed in the course of this study using conventional echocardiographic techniques. Size and systolic function were both evaluated in accordance with the recommendations for chamber quantification.7

Reproducibility of tricuspid annular motion measurements
To determine the degree of interobserver and intraobserver variability, TAM measurements were performed by two independent observers in 28 randomly selected patients and normal controls at two different sessions. The inter- and intra-observer reproducibility was calculated using unsigned relative errors [2 x |A – B| / (A + B), where A and B were the repeated measurements of the same method].15 Statistical analysis of reproducibility of methods was based on comparisons of the absolute values of relative errors using Mann–Whitney test. P-value <0.05 was considered statistically significant.

Statistical analysis
Continuous variables were summarized as means ± SD. Differences in continuous variables between patients with MFS and controls were investigated using t-test for independent samples, adjusting for unequal variances when appropriate. Categorical variables were expressed as absolute numbers and percentages. The statistical test in these cases was the {chi}2 test.

In addition, for each M-mode method (standard M-mode, anatomical M-mode, and colour anatomical M-mode) and TDI technique, the displacement from the free lateral RV wall was tested using multiple regression analysis to detect differences between patients with MFS and controls, adjusting for potential confounders. dp/dt was also tested following the same approach.

β-Blockers,16 age, and sex17 are known confounders and therefore we adjusted for these in all regression analyses. Further investigation was also carried out to assess the existence of other possible confounders. By keeping MFS diagnosis, β-blockers, age, and sex always within the models, both heart rate (HR) and pulmonary artery systolic pressure (PASP) were revealed as additional confounding variables but only for tricuspid annular displacement. Consequently, the model for the displacement from the free lateral RV wall using TDI and the model for dp/dt included only the MFS diagnosis, β-blockers, age, and sex. However, the model for the displacement measurements from the free lateral RV wall using the three M-mode methods was additionally adjusted for HR and PASP.

Finally, we performed meta-analyses in order to assess the overall effect of all these confounders on the results obtained from the three M-mode methods. By assuming these methods to be three separate experiments measuring the same underlying parameter, TAM, meta-analysis was considered to be both a valid and an appropriate technique.

The statistical analysis was performed using STATA.18


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Funding
 References
 
Subjects’ characteristics
Baseline demographic and clinical characteristics of both groups are presented in Table 1. Heart rate was statistically lower in patients with MFS than in controls. No statistical differences were observed in the other described variables between both groups.


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  		Table 1 Baseline characteristics for Marfan syndrome patients and controls

 
Right heart and valves
Values for the right heart size, RV thickness, and systolic blood flow velocities across the right heart valves are shown in Table 2. Right ventricle diameters obtained from the four-chamber view at basal and mid-levels in the end-diastole were significantly larger in MFS patients when compared with controls. Right ventricle end-diastolic size evaluated from the short-axis view at mid-level was also significantly larger in patients with MFS in comparison with controls. All these measurements remained statistically significant after correction for BSA. On the other hand, basal four-chamber LV end-diastolic diameter indexed for BSA showed no differences between the study groups. Consequently, RV/LV ratio was increased in MFS in comparison with controls. Right ventricle thickness measured from the sub-xiphoid view showed no differences in either group. Right atrial area measured in the four-chamber apical view was found increased in patients with MFS even after being indexed to BSA. Similarly, the PA size was also found to be significantly larger in MFS patients in comparison with controls. After correction for BSA, this difference remained statistically significant. Inferior vena cava size showed no difference in both groups.


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  		Table 2 Echocardiographic parameters in Marfan syndrome patients and controls

 
With regard to forward blood flow velocities across the pulmonary and tricuspid valves, pulmonary blood flow was decreased in MFS patients, whereas no statistical difference was noted in TR flow between the two groups. None of the study subjects had more than mild tricuspid and/or pulmonary regurgitation.

Right ventricle function
Right ventricle function parameters evaluated by two-dimensionally targeted M-mode techniques, Doppler, and TDI are summarized in Table 3. Systolic TAM obtained from the lateral side of the tricuspid annulus using M-mode, anatomical M-mode, and colour anatomical M-mode was significantly reduced in patients with MFS. In all methods, multiple regression analyses demonstrated that the presence of MFS was associated with reduced TAM. Heart rate also showed a statistically significant negative association with TAM. Age was found to be positively correlated with RV long-axis systolic function, whereas PASP was positively correlated only in M-mode technique. Meta-analysis of our results confirmed that MFS patients had reduced TAM when compared with controls (results of meta-analysis are shown in Table 4). The rate of pressure rise in RV (dp/dt) in systole was significantly lower in MFS patients in comparison with controls. Similarly, systolic velocities assessed by TDI were also reduced in MFS patients (Table 3).


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  		Table 3 Tricuspid annular motion measurements by M-mode techniques, tissue Doppler imaging, and dp/dt in Marfan syndrome patients and controls

 


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  		Table 4 Results of multiple regression analysis and overall estimates of the effect of various clinical characteristics on tricuspid annular motion measurements using M-mode techniques

 


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  		Table 5 Tricuspid annular motion measurements by M-mode techniques, tissue Doppler imaging, and dp/dt

 
Within the group of 29 patients who had known FBN1 mutations, it was not possible to demonstrate correlation between impaired RV long-axis systolic function and the type or location of these mutations.

Left ventricle function
With regard to conventional echocardiographic measurements (Table 6), dimensional measurements in diastole and systole were not significantly different between the patients and normal controls. After correcting for age and BSA using Henry’s regression equations, LV end-diastolic diameters expressed as percentage of the predicted value were significantly higher in patients with MFS in comparison with normal controls. However, none of the patients fulfilled the criteria for dilated cardiomyopathy. Ejection fraction evaluated by biplane Simpson’s method was found significantly reduced in MFS, although it was within the normal range. Fractional shortening was comparable between the study groups.


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  		Table 6 Left ventricle conventional echocardiographic measurements for Marfan syndrome patients and controls

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Funding
 References
 
This study was directed by our clinical observation that the role of RV function is underestimated in patients with MFS. Despite its complex morphology, the function of the RV is comparable with that of the LV.19 The contribution of the RV to maintaining the cardiac output is equally important to that of the LV. In the literature, there are a few case reports relating to RV function in MFS.20,21 To the best of our knowledge, there are no systematic studies on RV systolic function in patients with MFS.

This study is the first to assess RV systolic function and report mild, though statistically significant RV impairment in unoperated patients with MFS. Impaired RV systolic function should be considered primary in our patients, as coexisting diseases which could cause secondary ventricular functional abnormalities have been excluded.

Our data showed a slower increase in the slope of the tricuspid regurgitation velocity curve when compared with controls. Trivial or mild tricuspid regurgitation was present in all our patients and controls, which enabled recordings of systolic regurgitant jet and subsequent dp/dt calculation. dp/dt evaluation by continuous wave Doppler echocardiography represents a validated method which provides non-invasive information concerning biventricular systolic function.12,22 In our study, slower increase in systolic tricuspid regurgitant jet velocity was indicative of a slower rise in the systolic pressure within the RV.

In addition, TAM constitutes another well-established, quick but still reliable echocardiographic technique for assessing RV systolic function. Kaul et al.8 showed that TAM measurements obtained from the four-chamber view using two-dimensionally targeted M-mode echocardiography accurately reflected RV systolic function in normal subjects and patients with coronary heart disease. Although TAM does not take account of the total RV function during systole, it is closely correlated with RV EF obtained by nuclear angiography.8,23 We therefore decided to include in our investigation this echocardiographic method to assess systolic long-axis function in patients with MFS and healthy volunteers. In this study, the assessment of TAM showed a statistically significant decrease in RV systolic long-axis function in patients with MFS vs. controls. All three M-mode techniques used to measure TAM provided values comparable with each other.

Sanchez-Quintana et al.24 reported that the RV wall in the normal heart is arranged from the base towards the apex in two layers; one superficial layer with fibres running horizontally and another subendocardial layer where fibres run longitudinally. Immunohistochemical data obtained from tissue samples of human and rodent hearts revealed that fibrillin-1 is a major supporting tissue protein in the myocardium.25,26 Fibrillin-1-positive fibres were oriented in the longitudinal axis of cardiomyocytes; this spatial arrangement is indicative of the important function of the fibrillin-1-rich microfibrils in transmitting the forces of myocardial contraction from myocytes to the extracellular supporting tissue framework.

Meta-analysis of TAM measurements showed that MFS was significantly associated with reduced systolic long-axis function. Heart rate also showed a statistically negative correlation with TAM. Twenty-two out of 66 patients (33%) were on prophylactic treatment with β-blockers. After adjusting for β-blocker therapy, patients with MFS had a slower HR than controls in our series. This could be attributed to intrinsic abnormalities of the conduction system in MFS. More studies are needed to histologically define the structure of conductive tissue and its surrounding extracellular matrix in MFS. According to the Starling effect, bradycardia increases the end-diastolic fibre length, which leads to enhanced length-dependent activation of actin and myosin cross-bridges in the cardiac myocytes and a greater contractility. Despite the slower HR in MFS patients, the RV systolic long-axis function was found impaired.

In our series, age had a significant positive correlation with TAM. Our age group ranged between 15 and 58 years. Fifty-eight healthy subjects out of 61 (95%) and 55 MFS patients out of 66 (83%) were under the age of 45 years. This correlation is similar to that reported by Kukulski et al.17 on RV systolic long-axis function in normal individuals.

Meta-analysis also showed that PASP was positively correlated with TAM. Pulmonary artery systolic pressure measurements were within the normal range in both groups. If we assume that the RV in MFS is fibrillin-1-deficient, even normal values of PASP could impose a significantly increased afterload. In our series, MFS patients had increased RV size, suggesting that the RV attempts to compensate for increased afterload by the Frank–Starling mechanism. In contrast, the positive correlation observed between PASP and TAM in the control group could be explained by increased contractility. Despite the suggested compensatory mechanism in MFS, the RV long-axis systolic function was reduced in patients in comparison with the controls. Follow-up studies are needed to monitor potential changes in afterload with time and to assess the impact on the RV long-axis systolic function in patients with MFS.

The RV/LV ratio, which was significantly increased in our MFS patients, is a useful and sensitive measurement to detect and monitor RV dilatation. This calculation is often used to evaluate RV dysfunction and prognosis in various clinical conditions such as pulmonary embolism, congenital heart disease, and/or coronary heart disease.27–29

TDI to assess tricuspid annular velocities represents another reliable echocardiographic technique to assess RV systolic function. In the present study, reduced TDI velocities in systole were indicative of RV systolic dysfunction in MFS.

This study also demonstrated statistically significant LV systolic impairment in MFS patients.

In the past 10 years, exciting experimental studies in fibrillin-1-deficient mice have led to the expansion of our knowledge about the structure and assembly of fibrillin-1 microfibrils and its role in the TGF-β regulation and cardiovascular system.2 Dietz et al. report reduced pre-load-recruitable stroke work in the mouse model, which was correlated with increased TGF-β signalling (personal communication). In view of these findings, fibrillin-1 deficiency in the myocardium is likely to be responsible for the observed reduced RV systolic function in our study.

Limitations
Two-dimensionally targeted M-mode imaging is commonly used to assess TAM in everyday clinical practice. However, this technique measures only the overall systolic excursion of the RV free lateral wall towards the apex. Strain and strain rate echocardiography could better quantify changes in regional RV contractile function in MFS.

β-Blocker treatment could affect measurements of TAM, dp/dt, and TDI velocities. Vogel et al.16 demonstrated the impairment of RV contractility with the use of esmolol. However, our analysis showed no differences between patients on and off β-blockers for these values. In contrast, measurements obtained from controls and MFS patients without treatment showed statistically significant differences (Table 5).

In our study, there was a confirmed causative FBN1 mutation in 29 patients. This number of genotyped patients was not sufficient to link RV systolic function with a specific type or location of FBN1 mutation. In a further study, genotypic identification of all patients may provide enough data to correlate FBN1 mutations to RV dysfunction.

In conclusion, our study revealed mild but statistically significant RV systolic dysfunction in patients with MFS. The assessment of RV systolic function should be included in the examination of cardiac function in all patients with MFS. A number of alternative echocardiographic techniques are presently available to allow a clinician to evaluate RV systolic function and monitor the observed abnormalities over time in patients with MFS.


   Funding
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
References
 
This study was funded by the Henry Smith Charity through the Marfan Trust.


   Acknowledgements
 
We specially thank Professor Robert H. Anderson for his constructive contribution to our research. His leading expertise in cardiac anatomy was invaluable for our understanding of biventricular myocardial architecture. We also acknowledge the full support given to us by Mr Simon Robson of GE Medical Systems. Moreover, we are grateful to St George’s, University of London and St George’s Hospital NHS Trust for their support, enabling the authors to organize and complete this research project.

This study was performed at St George’s University of London and St George’s Hospital NHS Trust, London, UK.

Conflict of interest: none declared.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
 References
 

  1. Pyeritz RE, Dietz HC. Marfan Syndrome and Other Microfibrillar Disorders. In: Connective Tissue and Its Heritable Disorders—Royce PM, Steinmann B, eds. (2003) 2nd ed. Wiley-Liss, Inc. 585–626.
  2. Ramirez F, Dietz HC. Marfan syndrome: from molecular pathogenesis to clinical treatment. Curr Opin Genet Dev (2007) 17:252–8.[CrossRef][Web of Science][Medline]
  3. Dietz HC, Loeys B, Carta L, Ramirez F. Recent progress towards a molecular understanding of Marfan syndrome. Am J Med Genet C Semin Med Genet (2005) 139:4–9.
  4. Chatrath R, Beauchesne LM, Connolly HM, Michels VV, Driscoll DJ. Left ventricular function in the Marfan syndrome without significant valvular regurgitation. Am J Cardiol (2003) 91:914–6.[CrossRef][Web of Science][Medline]
  5. Meijboom LJ, Timmermans J, van Tintelen JP, Nollen GJ, De Backer J, van den Berg MP, et al. Evaluation of left ventricular dimensions and function in Marfan’s syndrome without significant valvular regurgitation. Am J Cardiol (2005) 95:795–7.[CrossRef][Web of Science][Medline]
  6. De Backer JF, Devos D, Segers P, Matthys D, Francois K, Gillebert TC, et al. Primary impairment of left ventricular function in Marfan syndrome. Int J Cardiol (2006) 112:353–8.[CrossRef][Web of Science][Medline]
  7. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification. Eur J Echocardiogr (2006) 7:79–108.[Abstract/Free Full Text]
  8. Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricular function using two-dimensional echocardiography. Am Heart J (1984) 107:526–31.[CrossRef][Web of Science][Medline]
  9. Kjaergaard J, Petersen CL, Kjaer A, Schaadt BK, Oh JK, Hassager C. Evaluation of right ventricular volume and function by 2D and 3D echocardiography compared to MRI. Eur J Echocardiogr (2006) 7:430–8.[Abstract/Free Full Text]
  10. De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet (1996) 62:417–26.[CrossRef][Web of Science][Medline]
  11. Comeglio P, Johnson P, Arno G, Brice G, Evans A, Aragon-Martin J, et al. The importance of mutation detection in Marfan syndrome and Marfan-related disorders: report of 193 FBN1 mutations. Hum Mutat (2007) 28:928.[Medline]
  12. Oh JK, Seward JB, Tajik AJ. Doppler Echocardiography and Color Flow Imaging: Comprehensive Noninvasive Hemodynamic Assessment. In: The echo manual—Oh JK, Seward JB, Tajik AJ, eds. (2006) 3rd ed. Lippincott Williams & Wilkins-a Wolters Kluwer business. 77.
  13. Carlhäll C-J, Hatle L, Lindström L, Wranne B, Nylander E. A new method for measuring atrioventricular plane displacement with M-mode echocardiography for assessment of systolic ventricular function. Clin Physiol (1999) 19:197–197.
  14. Quinones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr (2002) 15:167–84.[CrossRef][Web of Science][Medline]
  15. Savelieva I, Aytemir K, Hnatkova K, Camm AJ, Malik M. Short-, mid-, and long-term reproducibility of the atrial signal-averaged electrocardiogram in healthy subjects: comparison with the conventional ventricular signal-averaged electrocardiogram. Pacing Clin Electrophysiol (2000) 23:122–7.[CrossRef][Medline]
  16. Vogel M, Schmidt MR, Kristiansen SB, Cheung M, White PA, Sorensen K, et al. Validation of myocardial acceleration during isovolumic contraction as a novel noninvasive index of right ventricular contractility: comparison with ventricular pressure–volume relations in an animal model. Circulation (2002) 105:1693–9.[Abstract/Free Full Text]
  17. Kukulski T, Hubbert L, Arnold M, Wranne B, Hatle L, Sutherland GR. Normal regional right ventricular function and its change with age: a Doppler myocardial imaging study. J Am Soc Echocardiogr (2000) 13:194–204.[Web of Science][Medline]
  18. Stata Corporation STATA/SE 9.2 Statistics/Data Analysis (2007) College Station, TX: Stata Corporation. [computer program].
  19. Dell’Italia LJ, Santamore WP. Can indices of left ventricular function be applied to the right ventricle? Prog Cardiovasc Dis (1998) 40:309–24.[CrossRef][Web of Science][Medline]
  20. Henderson JW. Marfan’s syndrome: report of a case with a congenital aneurysm of the coronary sinus and perforation into the right ventricle. J Indiana State Med Assoc (1961) 54:325–8.[Web of Science][Medline]
  21. Leitch AG, Caves PK. A case of Marfan’s syndrome with absent right coronary artery complicated by aortic dissection and right ventricular infarction. Thorax (1975) 30:352–4.[Abstract/Free Full Text]
  22. Bargiggia GS, Bertucci C, Recusani F, Raisaro A, de Servi S, Valdes-Cruz LM, et al. A new method for estimating left ventricular dP/dt by continuous wave Doppler-echocardiography. Validation studies at cardiac catheterization. Circulation (1989) 80:1287–92.[Abstract/Free Full Text]
  23. Ueti OM, Camargo EE, Ueti Ade A, de Lima-Filho EC, Nogueira EA. Assessment of right ventricular function with Doppler echocardiographic indices derived from tricuspid annular motion: comparison with radionuclide angiography. Heart (2002) 88:244–8.[Abstract/Free Full Text]
  24. Sanchez-Quintana D, Anderson RH, Ho SY. Ventricular myoarchitecture in tetralogy of Fallot. Heart (1996) 76:280–6.[Abstract/Free Full Text]
  25. Vracko R, Thorning D, Frederickson RG. Spatial arrangements of microfibrils in myocardial scars: application of antibody to fibrillin. J Mol Cell Cardiol (1990) 22:749–57.[CrossRef][Web of Science][Medline]
  26. Bouzeghrane F, Reinhardt DP, Reudelhuber TL, Thibault G. Enhanced expression of fibrillin-1, a constituent of the myocardial extracellular matrix in fibrosis. Am J Physiol Heart Circ Physiol (2005) 289:H982–H991.[Abstract/Free Full Text]
  27. Ghaye B, Ghuysen A, Willems V, Lambermont B, Gerard P, D’Orio V, et al. Severe pulmonary embolism:pulmonary artery clot load scores and cardiovascular parameters as predictors of mortality. Radiology (2006) 239:884–91.[Abstract/Free Full Text]
  28. Navabi Shirazi MA, Ghavanini AA, Sajjadi S. Early postoperative results after total correction of tetralogy of Fallot in older patients: is primary repair always justified? Pediatr Cardiol (2001) 22:238–41.[CrossRef][Web of Science][Medline]
  29. Sharpe DN, Botvinick EH, Shames DM, Schiller NB, Massie BM, Chatterjee K, et al. The noninvasive diagnosis of right ventricular infarction. Circulation (1978) 57:483–90.[Abstract/Free Full Text]

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