Skip Navigation


European Journal of Echocardiography Advance Access originally published online on June 20, 2008
European Journal of Echocardiography 2008 9(6):849-854; doi:10.1093/ejechocard/jen192
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
9/6/849    most recent
jen192v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Afonso, L.
Right arrow Articles by Sandidge, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Afonso, L.
Right arrow Articles by Sandidge, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Takotsubo cardiomyopathy: pathogenetic insights and myocardial perfusion kinetics using myocardial contrast echocardiography

Luis Afonso*, Khaled Bachour, Khaled Awad and Greg Sandidge

Division of Cardiology, 3990 John R, 8 Brush, Harper University Hospital, Wayne State University, Detroit Medical Center, Detroit, MI 48201, USA

Received 19 March 2008; accepted after revision 30 May 2008; online publish-ahead-of-print 20 June 2008.

* Corresponding author. Tel: +1 313 745 2620; fax: +1 313 993 8627. E-mail address: lafonso{at}med.wayne.edu


   Abstract
Top
 Abstract
Case 1
 Case 2
 Case 3
 Results
 Discussion
 Conclusion
 Supplementary data
 References
 
Transient apical ballooning syndrome or Takotsubo cardiomyopathy (TC) is a novel acute cardiac syndrome, characterized by regional systolic dysfunction involving the apex and mid-ventricular segments, with hyperkinesis of the basal segments. Mid-ventricular ballooning cardiomyopathy (MVBC) is a recently recognized variant of TC. Both disorders share the same precipitating factors, clinical features and course; however, unlike TC, MVBC is characterized by ballooning and akinesis of the mid-ventricular segments with hypercontractility of the basal and apical segments. While the precise pathogenetic mechanism of this disorder remains elusive, microvascular dysfunction from excessive catecholamine release has been implicated. We report findings on regional contractile dysfunction (strain imaging), myocardial blood flow (semi-quantitative), and perfusion kinetics using myocardial contrast echocardiography in a series of three illustrative cases of TC.

Keywords: Takotsubo cardiomyopathy; Myocardial contrast echocardiography; Myocardial perfusion; Apical ballooning syndrome; Microvascular


   Case 1
Top
 Abstract
 Case 1
Case 2
 Case 3
 Results
 Discussion
 Conclusion
 Supplementary data
 References
 
A 46-year-old male was admitted with status epilepticus. The electrocardiogram (ECG) revealed sinus tachycardia and T-wave inversion in the lateral leads. Peak Troponin I (cTnI) was 0.55 ng/mL (<0.4). A 2D-echocardiogram showed severe left ventricular (LV) systolic dysfunction, an ejection fraction (EF) of 20%, akinesis of the mid-ventricular segments and preserved contractility of the apex and basal segments, suggestive of mid-ventricular ballooning cardiomyopathy (MVBC), a variant of Takotsubo cardiomyopathy (TC). Coronary angiography was normal. On 2D strain imaging, akinesis and paradoxical strain of the mid-ventricular segments was noted (Figure 1, Supplementary data online, video 1). Myocardial contrast echocardiography (MCE) revealed preserved perfusion and contrast wash-in in the apical and basal segments of the left ventricle with delayed replenishment evident in the mid-segments. Time intensity curves showed significant attenuation of plateau video intensity (VI) consistent with decreased myocardial blood volume (MBV) and flow in the mid-segments (Figure 2A and B, Supplementary data online, video 2). Plateau VI after wash-in curve fitting assessed using triggered intervals in end-systole (when the arterioles and veins are devoid of blood) was attenuated in the mid-segments relative to the base and apex (Figure 3), representing diminished capillary cross-sectional volume in these areas. A repeat echocardiogram performed 4 weeks later revealed complete resolution of systolic dysfunction (EF, 50–55%) and regional wall motion abnormalities.


Figure 1
View larger version (54K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 1 Two-dimensional longitudinal strain curves and corresponding parametric image (2D and colour-anatomic M-mode) showing dyskinesis (paradoxical strain) of the mid-inferior septum (light blue trace), and severe hypokinesis of the mid-lateral wall (dark blue trace) with preserved contractility at the apex and base.

 


Figure 2
View larger version (66K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 2 (A) Contrast replenishment traces in the basal inferior septum (yellow), mid-inferior septum (blue), apex (red), and mid-inferolateral wall (green), timed immediately following a high-energy ultrasound pulse. Fitted replenishment curves are then used to calculate A and β for each segment. (B) Representative regions of interest (ROI) in the myocardium where replenishment was assessed.

 


Figure 3
View larger version (54K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 3 Wash in curve fitting using triggering intervals depicting attenuated plateau contrast levels in the midventricular segments during end-systole (myocardium devoid of arteriolar and venous blood), a surrogate indicator of reduced capillary blood volume in these areas.

 

   Case 2
Top
 Abstract
 Case 1
 Case 2
Case 3
 Results
 Discussion
 Conclusion
 Supplementary data
 References
 
A 38-year-old premenopausal female with history of chronic obstructive pulmonary disease, severe wheezing, and hypoxia was intubated upon arrival. ECG at presentation showed sinus tachycardia, and right bundle branch block, but no ischaemic changes. She was admitted to the intensive care unit with a diagnosis of chronic obstructive pulmonary disease exacerbation. Initial serum cTnI was 1.34 ng/mL. Two-dimensional echocardiogram showed hypokinesis, involving the LV apex and distal segments. Cardiac catheterization revealed normal coronary arteries. MCE revealed decreased capillary blood volume and flow in the apical and mid-ventricular segments and sparing of the basal segments. The patient’s respiratory status improved, and she was extubated and discharged after complete clinical recovery. Complete resolution of regional and global systolic dysfunction (EF, 65%) was evident on a follow-up surface echocardiogram done 2 months post-discharge.


   Case 3
Top
 Abstract
 Case 1
 Case 2
 Case 3
Results
 Discussion
 Conclusion
 Supplementary data
 References
 
A 52-year-old postmenopausal female admitted for further workup of her chest tightness. The initial ECG was remarkable for sinus tachycardia, T-wave inversion in the lateral leads, and prolongation of the QT interval. On subsequent ECG’s, the T-wave inversion spread to involve the inferior leads and the troponin peaked at 2.0 ng/mL. A 2D-echo revealed dilatation and akinesis involving apical and mid-ventricular segments, hyperkinesis of the basal segments, and an EF of 20%, findings consistent with TC. Cardiac catheterization revealed no abnormalities. MCE showed a decrease in capillary blood flow and volume in the akinetic areas with delayed contrast replenishment (wash-in post-high power flash), sparing the basal segments. A repeat 2D echo, 2 weeks later, revealed an EF of 45%, resolution of the apical dilatation with mild residual apical and mid-ventricular hypokinesis. A repeat MCE study showed near-normalization of perfusion parameters in affected areas. None of the patients described in our series had evidence of right ventricular systolic dysfunction.

Qualitative and quantitative assessment
Myocardial contrast echocardiography was performed using bolus injections of Definity (Bristol-Myers Squibb, Billerica, MA, USA) and low mechanical index real-time harmonic imaging (Vivid & scanner, GE Vingmed). Time intensity curves were sampled offline [regions of interest (ROI) of 6 mm x 3 mm], using the Echo PAC work station. Images for 2D strain (speckle tracking) were acquired at a frame rate of 70–80 frames per second. Two-dimensional strain entails spatial and temporal tracking of adjacent naturally occurring acoustic markers or ‘speckles’ from standard black and white echocardiographic images. Deformation is calculated on a frame–frame analysis of speckle displacement, yielding angle-independent parameters of myocardial contraction, namely longitudinal, transverse, and radial strain and strain rate.1


   Results
Top
 Abstract
 Case 1
 Case 2
 Case 3
 Results
Discussion
 Conclusion
 Supplementary data
 References
 
A summary of mean bubble velocity represented by the slope of the replenishment curve (β) and plateau intensity values (A) for representative ROI’s in the myocardium are summarized in Table 1. Corresponding peak longitudinal 2D strain values (manual mapping in respective ROI’s) are also depicted.


View this table:
[in this window]
[in a new window]

  		Table 1 A and β values for representative areas of interest in the myocardium

 

   Discussion
Top
 Abstract
 Case 1
 Case 2
 Case 3
 Results
 Discussion
Conclusion
 Supplementary data
 References
 
Takotsubo cardiomyopathy is a novel syndrome characterized by transient, acute-onset ventricular systolic dysfunction, in the absence of epicardial coronary artery disease. Although predominantly described in postmenopausal women, reports of this entity in younger adults and children exist in the literature.2–5 Emotional or physical stress is the usual triggering event. The most common clinical presentations of TC are chest pain (68%) and dyspnea (18%) while the most frequent electrocardiographic findings are ST-segment elevation (81%), followed by T-wave abnormalities (64%) and Q waves (31%).3 Histological findings on endomyocardial biopsy include focal myocytolysis, mononuclear infiltrates, and contraction band necrosis without evidence of myocarditis.6

Although the precise cause and mediators of myocardial injury in TC remain unclear, a host of pathophysiological mechanisms have been implicated, including epicardial multivessel spasm, microvascular spasm, acute coronary syndrome with reperfusion, myocarditis, and transient obstruction of the LV outflow tract. Multivessel spasm has been demonstrated inconsistently even following provocation,7–9 with intracoronary ergonovine or acetylcholine and probably does not explain MVBC, a variant of TC that spares the apex but affects the mid-ventricular segments10 (e.g. Case 1).

Excessive sympathetic stimulation and catecholamine release3,6,11 appear to be central to the pathogenesis of TC. Ueyama et al.12 induced transient LV apical ballooning in rats exposed to emotional stress but were unable to reproduce these effects after pre-treatment with {alpha}- and β-adrenoreceptor blockers. Plasma catecholamine and neuropeptide levels were significantly higher among patients with TC than among those with Killip class III myocardial infarction.6 Akashi et al.13 performed serial 123I-metaiodobenzlguanidine serial (123I-MIBG) myocardial scintigraphy in eight patients with TC during the index admission, and at 3 months follow-up. On the basis of heart–mediastinum ratios and higher radioisotope washout rates in the initial compared with follow-up scans, they suggested that cardiac hypersympathetic activity and neurogenic myocardial stunning could be the operant mechanisms in the genesis of TC. MIBG is structurally similar to norepinephrine and utilizes the same uptake and storage mechanisms. 123I-MIBG scintigraphy was developed to evaluate cardiac sympathetic nervous function (sympathetic nerve density), and a decreased uptake denotes adrenergic dysfunction.

Similarly, radiolabelled 123I-metyl-iodophenyl pentadecanoic acid (BMIPP) uptake is impaired in the setting of transient cardiac dysfunction, reflecting a reduction in myocardial long-chain fatty acid utilization. Using rest 201Tl and 123I-BMIPP dual-isotope myocardial SPECT imaging, Kurisu et al.14 reported a discrepancy between myocardial perfusion and fatty acid metabolism, further reinforcing the ‘myocardial stunning’ concept. Myocardial fatty acid metabolism was impaired to a greater extent than myocardial perfusion in the early stages and, although this discrepancy improved during follow-up, metabolic impairment persisted beyond resolution of systolic dysfunction.14 A reduction in regional glucose uptake out of proportion to the myocardial perfusion abnormality was also demonstrated in TC using 13N-ammonia (flow tracer) and 18F-fluorodeoxyglucose positron emission tomography, providing further corroborative evidence of myocardial stunning and microcirculatory disruption.15

Multiple factors modulate coronary blood flow including epicardial coronary diameter, antegrade perfusion pressure, vasospasm, wall stress, and the integrity of the coronary microcirculation. Microvascular function in TC has been showed to be deranged by several techniques including angiographic Thrombolysis In Myocardial Infarction trial (TIMI) frame count14 (reflecting increased coronary vascular resistance), TIMI myocardial perfusion grades,16 MCE,17,18 and coronary perfusion/flow reserve as assessed by nuclear imaging,19–21 transthoracic22 and intracoronary Doppler techniques.23–25

Myocardial contrast echocardiography can be rapidly performed by the bedside and repeated serially if needed, for monitoring myocardial perfusion. Upadya et al.18 first reported a perfusion defect in an elderly woman (using real-time low-mechanical index MCE) that resolved within 72 h. More recently, Azzareli et al.17 described a similar case and demonstrated normalization of the perfusion abnormalities during follow-up, using time intensity curves.17

Myocardial contrast echocardiography utilizes gas-filled microbubbles that are very effective in scattering ultrasound due to their very small radius (<5 µm), a property that also accounts for similarities between microbubble and erythrocyte rheology. Ultrasound scattered by microbubbles can be quantified using VI to evaluate the integrity of the microvasculature, particularly capillary flow and density.

For assessing resting capillary blood flow, a steady state of contrast infusion has to be first achieved. Subsequently, a high-energy ultrasound pulse(s) is delivered to destroy myocardial microbubbles, followed by low-mechanical index imaging to assess its rate of reappearance, a surrogate measure of erythrocyte velocity (1 mm s–1 at rest). The change in the VI over time is then fitted into a monoexponential curve that represents the replenishment phase of contrast flow, and from that curve several parameters are then derived. The relation between the change in the VI and time can be represented by the following function:



Formula

where y is the VI at time t, A is the plateau VI, and β is the rate constant that represents the rate of rise of VI.26 The value A is proportional to the microvascular cross-sectional area and MBV in the surveyed myocardium, whereas β correlates with the myocardial blood flow velocity within the myocardial region of interest.26

Our patients demonstrated significantly attenuated A and β values in affected myocardial regions compared with spared segments that manifested normal replenishment and contractile patterns (Table 1). The decreased MBV and velocity in affected segments is consistent with arteriolar vasoconstriction,27 resulting in a marked loss of capillary bed volume as evidenced by the end-systolic triggered plateau intensity wash in curves. The presence of normal epicardial coronary vessels and lack of conformity of contractile or perfusion abnormalities to known coronary artery distributions argue against epicardial spasm being the causative mechanism of microvascular dysfunction. Finally, the severity and extent of perfusion abnormalities (MCE) matched impairments in segmental contractile function (manual spatial mapping of video intensity) and improved in parallel during follow-up (Case 3). These and other data from the literature discussed above lend further credence to catecholamine-induced stunning as the primary underlying pathophysiological mechanism responsible for TC. However, it is still unclear whether myocardial stunning ensues from the hyperadrenergic state (accompanying arteriolar vasoconstriction and profound reduction of coronary flow) or from the direct toxic effects of catecholamine on myocytes. Finally, the vulnerability and predominant involvement of the LV apex is intriguing and needs to be addressed by future research.


   Conclusion
Top
 Abstract
 Case 1
 Case 2
 Case 3
 Results
 Discussion
 Conclusion
Supplementary data
 References
 
The pathophysiology of TC/MVBC remains poorly understood. First, our findings confirm that disruption of microvascular integrity appears to be the proximate underlying mechanism of contractile dysfunction in TC. Secondly, the attenuation of myocardial blood flow velocity seems to accompany a reduction in cross-sectional capillary bed volume in segments demonstrating contractile dysfunction. Finally, our illustrative cases also highlight the feasibility and unique ability of MCE to rapidly and inexpensively quantify myocardial perfusion, profile perfusion kinetics, and contractile abnormalities by the bedside. Technique simplicity allows for serial assessment of coronary flow, facilitating future research in the pathogenesis of this intriguing entity. To the best of our knowledge, these are the first reported cases of MVBC or TC to profile myocardial flow kinetics (qualitatively and semi-quantitatively) using MCE and contractile abnormalities with 2D (speckle tracking) strain imaging.


   Supplementary data
Top
 Abstract
 Case 1
 Case 2
 Case 3
 Results
 Discussion
 Conclusion
 Supplementary data
References
 
Supplementary data are available at European Journal of Echocardiography online.

Conflict of interest: none declared.


   References
Top
 Abstract
 Case 1
 Case 2
 Case 3
 Results
 Discussion
 Conclusion
 Supplementary data
 References
 

  1. Leitman M, Lysyansky P, Sidenko S, Shir V, Peleg E, Binenbaum M, et al. Two-dimensional strain—a novel software for real-time quantitative echocardiographic assessment of myocardial function. J Am Soc Echocardiogr (2004) 17:1021–9.[CrossRef][Web of Science][Medline]
  2. Maruyama S, Nomura Y, Fukushige T, Eguchi T, Nishi J, Yoshinaga M, et al. Suspected takotsubo cardiomyopathy caused by withdrawal of bupirenorphine in a child. Circ J (2006) 509–11.
  3. Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E. Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review. Eur Heart J (2006) 1523–9.
  4. Reuss CS, Lester SJ, Hurst RT, Askew JW, Nager P, Lusk J, et al. Isolated left ventricular basal ballooning phenotype of transient cardiomyopathy in young women. Am J Cardiol (2007) 99:1451–3.[CrossRef][Web of Science][Medline]
  5. Ramakrishna G, Ravi BS, Chandrasekaran K. Apical ballooning syndrome in a postoperative patient with normal microvascular perfusion by myocardial contrast echocardiography. Echocardiography (2005) 22:606–10.[CrossRef][Web of Science][Medline]
  6. Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med (2005) 352:539–48.[Abstract/Free Full Text]
  7. Akashi YJ, Nakazawa K, Kida K, Ryu S, Takagi A, Kishi R, et al. Reversible ventricular dysfunction (takotsubo cardiomyopathy) following polymorphic ventricular tachycardia. Can J Cardiol (2003) 449–51.
  8. Kurisu S, Sato H, Kawagoe T, Ishihara M, Shimatani Y, Nishioka K, et al. Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J (2002) 143:448–55.[CrossRef][Web of Science][Medline]
  9. Abe Y, Kondo M, Matsuoka R, Araki M, Dohyama K, Tanio H. Assessment of clinical features in transient left ventricular apical ballooning. J Am Coll Cardiol (2003) 41:737–42.[Abstract/Free Full Text]
  10. Hurst RT, Askew JW, Reuss CS, Lee RW, Sweeney JP, Fortuin FD, et al. Transient midventricular ballooning syndrome: a new variant. J Am Coll Cardiol (2006) 48:579–83.[Abstract/Free Full Text]
  11. Akashi YJ, Musha H, Kida K, Itoh K, Inoue K, Kawasaki K, et al. Reversible ventricular dysfunction takotsubo cardiomyopathy. Eur J Heart Fail (2005) 1171–6.
  12. Ueyama T, Kasamatsu K, Hano T, Yamamoto K, Tsuruo Y, Nishio I. Emotional stress induces transient left ventricular hypocontraction in the rat via activation of cardiac adrenoceptors: a possible animal model of ‘tako-tsubo’ cardiomyopathy. Circ J (2002) 66:712–3.[CrossRef][Web of Science][Medline]
  13. Akashi YJ, Nakazawa K, Sakakibara M, Miyake F, Musha H, Sasaka K. 123I-MIBG myocardial scintigraphy in patients with ‘takotsubo’ cardiomyopathy. J Nucl Med (2004) 1121–7.
  14. Kurisu S, Inoue I, Kawagoe T, Ishihara M, Shimatani Y, Nishioka K, et al. Myocardial perfusion and fatty acid metabolism in patients with tako-tsubo-like left ventricular dysfunction. J Am Coll Cardiol (2003) 41:743–8.[Abstract/Free Full Text]
  15. Bybee KA, Murphy J, Prasad A, Wright RS, Lerman A, Rihal CS, et al. Acute impairment of regional myocardial glucose uptake in the apical ballooning (takotsubo) syndrome. J Nucl Cardiol (2006) 13:244–50.[CrossRef][Web of Science][Medline]
  16. Elesber A, Lerman A, Bybee KA, Murphy JG, Barsness G, Singh M, et al. Myocardial perfusion in apical ballooning syndrome correlate of myocardial injury. Am Heart J (2006) 152. 469 e9–13.
  17. Azzarelli S, Giordano G, Galassi AR, Amico F, Giacoppo M, Argentino V, et al. Transient impairment of myocardial perfusion in a patient with apical ballooning syndrome. Int J Cardiol (2007) 118:e63–e65.[CrossRef][Medline]
  18. Upadya SP, Hoq SM, Pannala R, Alsous F, Tuohy E, Zarich S. Tako tsubo cardiomyopathy (transient left ventricular apical ballooning): case report of a myocardial perfusion echocardiogram study. J Am Soc Echocardiogr (2005) 18:883.
  19. Ito K, Sugihara H, Kawasaki T, Yuba T, Doue T, Tanabe T, et al. Assessment of ampulla (Takotsubo) cardiomyopathy with coronary angiography, two-dimensional echocardiography and 99mTc-tetrofosmin myocardial single photon emission computed tomography. Ann Nucl Med (2001) 351–5.
  20. Ito K, Sugihara H, Katoh S, Azuma A, Nakagawa M. Assessment of Takotsubo (ampulla) cardiomyopathy using 99mTc-tetrofosmin myocardial SPECT—comparison with acute coronary syndrome. Ann Nucl Med (2003) 115–22.
  21. Hadase M, Kawasaki T, Asada S, Kamitani T, Kawasaki S, Sugihara H. Reverse redistribution of Tc-99m tetrofosmin in a patient with ‘takotsubo’ cardiomyopathy. Clin Nucl Med (2003) 757–9.
  22. Ikeda E, Maekawa K, Kawamoto K, Fuke S, Takagaki K, Sato T, et al. Takotsubo cardiomyopathy manifesting as no reflow pattern in coronary flow by transthoracic Doppler echocardiography and prolonged recovery of regional left ventricular wall motion abnormality: a case report. J Cardiol (2006) 39–46.
  23. Yanagi S, Nagae K, Yoshida K, Matsumura Y, Nagashima E, Okada M, et al. Evaluation of coronary flow reserve using Doppler guide wire in patients with ampulla cardiomyopathy: three case reports. J Cardiol (2002) 305–12.
  24. Kume T, Akasaka T, Kawamoto T, Yoshitani H, Watanabe N, Neishi Y, et al. Assessment of coronary microcirculation in patients with takotsubo-like left ventricular dysfunction. Circ J (2005) 934–9.
  25. Nishikawa S, Ito K, Adachi Y, Katoh S, Azuma A, Matsubara H. Ampulla (‘takotsubo’) cardiomyopathy of both ventricles: evaluation of microcirculation disturbance using 99mTc-tetrofosmin myocardial single photon emission computed tomography and Doppler guide wire. Circ J (2004) 1076–80.
  26. Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM, Kaul S. Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation (1998) 97:473–83.[Abstract/Free Full Text]
  27. Wei K, Kaul S. The coronary microcirculation in health and disease. Cardiol Clin (2004) 22:221–31.[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Eur Heart JHome page
G. Barletta, S. Del Pace, M. Boddi, R. Del Bene, C. Salvadori, B. Bellandi, M. Coppo, E. Saletti, and G. F. Gensini
Abnormal coronary reserve and left ventricular wall motion during cold pressor test in patients with previous left ventricular ballooning syndrome
Eur. Heart J., August 21, 2009; (2009) ehp325v1.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
9/6/849    most recent
jen192v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Afonso, L.
Right arrow Articles by Sandidge, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Afonso, L.
Right arrow Articles by Sandidge, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?