Evaluation of transient apical ballooning with cardiac magnetic resonance imaging and 31-phosphorous magnetic resonance spectroscopy

International Journal of Cardiology 118 (2007) 249 – 252 www.elsevier.com/locate/ijcard

Letter to the Editor

Evaluation of transient apical ballooning with cardiac magnetic resonance imaging and 31-phosphorous magnetic resonance spectroscopy G. Klug a , C. Wolf b , T. Trieb b , M. Frick a , A. Koehler a , M.F. Schocke b , W. Jaschke b , O. Pachinger a , B. Metzler a,⁎ a

Clinical Division of Cardiology, Innsbruck Medical University, Anichstraβe 35, A-6020 Innsbruck, Austria b Radiology Department I, Innsbruck Medical University, Austria Received 2 March 2006; accepted 28 June 2006 Available online 16 October 2006

Abstract Apical ballooning is an increasingly reported transient cardiomyopathy with yet unknown origin. In this study 2 cases of apical ballooning are described in whom we used a combined approach of cardiac magnetic resonance imaging (CMR) and 31-Phosphorous magnetic resonance spectroscopy (31P MRS). Electrocardiogram showed ST abnormalities and cardiac serum markers were mildly elevated, but CAG demonstrated smooth coronary arteries. Cine-CMR revealed severe apical akinesia and significantly decreased ejection fraction. Furthermore we detected reduced myocardial phosphocreatine to beta-ATP (PCr/b-ATP) ratios during the first week of acute disease. After 1 week we observed an improvement of PCr/b-ATP ratios by 68% and 34%, which was associated with an increase in left ventricular function. Our data suggest that 31P MRS might be a valuable tool in the evaluation of apical ballooning, but larger cohorts are needed to improve the understanding of metabolic changes during transient apical ballooning. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Transient apical ballooning; Cardiac magnetic resonance; Magnetic resonance spectroscopy

1. Introduction Transient apical ballooning is an increasingly reported stress-induced cardiomyopathy. It mostly presents clinically as an ST-elevation infarction, but coronary angiography (CAG) shows, by definition, no critical lesions [1]. Diagnostic criteria for transient apical ballooning are (a) reversible balloon-like motion abnormalities of apical and mid-segments with hypercontraction of the basal segments, (b) ST-T segment abnormalities, (c) absence of obstructive coronary disease and (d) absence of head injuries, pheochromocytoma or other cardiac causes [1]. The pathogenesis of apical ballooning is yet unknown. ⁎ Corresponding author. Tel.: +43 512 504 81315; fax: +43 512 504 23264. E-mail address: [email protected] (B. Metzler). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.06.060

Cine-MRI represents the gold standard of in-vivo examination of cardiac function and morphological details. First-pass perfusion imaging detects impaired coronary flow reserve. Late contrast enhanced (LE-CMR) sequences are described to be able to detect nonviable myocardium, myocyte damages and myocardial scarring [2]. Magnetic resonance spectroscopy (MRS) is a unique tool to investigate human myocardial high-energy phosphate (HEP) metabolism in vivo. PCr/b-ATP ratio examined by MRS is mainly used as an index for cardiac energy metabolism. Previous studies suggested “normal” PCr/ATP ratios to be around 1.6 to 2.0 [3,4], moderately decreasing with age [3]. Decreased PCr/ATP ratios were also described e.g. in ischemic and failing hearts [4]. The aim of this small case study is to evaluate the value of 31P MRS in improving the understanding of the pathogenesis of transient apical ballooning.

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2. Methods 2.1. Study population Two female patients with suspected acute coronary syndrome were diagnosed as suffering from transient apical ballooning. In both cases CAG performed after admission showed no coronary artery disease. First combined CMR/MRS examination was arranged 5 h after CAG. CMR/MRS follow-up was arranged on days 6 and 9 (patient 1) and on days 5 and 6 (patient 2), respectively. 2.2. Case report patient 1 A 66-year-old woman was admitted to cardiac care unit because of retrosternal pain and syncope during mild physical exercise. At admission electrocardiogram (ECG) showed sinus rhythm and ST-segment elevation in leads V3–V6 (Fig. 1). For laboratory findings see Table 1. Patient 2 presented similar to patient 1 (Table 1). 2.3. CMR protocol On a 1.5 T MR scanner (Magnetom Vision Symphony, Siemens Erlangen, Germany) Cine-MR images were acquired using breathhold ECG-triggered cine bright blood sequences. Evaluation was performed on standard software (ARGUS, Siemens Erlangen, Germany). CE-CMR sequences were performed on the same scanner. Study protocol contained T1-w Turbo Spin Echo (T1w-TSE), first-pass and late-enhancement sequences with the use of Gadodiamide (Gd, OMNISCAN®, GE Healthcare, UK) con-

Table 1 Characterisation of transient apical ballooning by means of laboratory and CMR/MRS parameters Study variable

Patient 1

Patient 2

Day 1

Day 9

Day 1

Day 5

CK, U/l cTnT, μg/l Cine-MR EF, % EDV, ml/m2 ESV, ml/m2 SV, ml/m2 SWT (mean) Basal, % Mid, % Apical, % Gd first-pass CMR Myocardial perfusion Gd LE CMR Gdhyperenhancement 31P MRS PCr/b-ATP ratio

165 0.21

Normal Normal

277 0.193

Normal Normal

28 76 54 21

41 60 35 25

33 56 35 18

42 67 38 28

59.0 ± 7.9 0.4 ± 7.0 −2.8 ± 6.4

40.9 ± 4.8 9.4 ± 5.1 56.0 ± 6.5

69.0 ± 12.5 89.7 ± 6.7 33.8 ± 17.4 35.4 ± 8.2 − 8.9 ± 6.7 28.4 ± 17.0

Normal

Normal

Normal

normal

Weak diffuse

Decreased

Weak diffuse Little

1.08 ± 0.09

1.83 ± 0.14 1.32 ± 0.16 1.84 ± 0.19

Data is presented as mean ± S.E. Abbreviations: CK: creatine kinase, cTnT: cardiac troponin T, EF: ejection fraction, EDV: end-diastolic volume, ESV: end-systolic volume, SV: stroke volume, SWT: segmental systolic wall thickening, Gd: gadolinium, CMR: cardiac magnetic resonance, LE: late enhancement, 31P MRS: 31phosphorous magnetic resonance spectroscopy.

trast medium. 0.01 mmol/kg of Gd were administered as a bolus to obtain first-pass sequences. Thereafter we applied another bolus 0.01 mmol/kg for LE sequences. LE images were acquired after 10 min. Evaluation was performed qualitatively.

Fig. 1. CMR (cine bright blood, A) and ventriculographic (right anterior oblique, B) images during end-diastole. During end-systole imaging (C, D) reveals lack of SWT in apical and mid-areas of the left ventricle (dark arrows) and basal hyperkinesia (light arrows) presenting as the typical picture of an apical ballooning (patient 1). (E) ECG of patient 1 at admission. ST-segment elevations in V3–V6 are mimicking an anterior myocardial infarction.

G. Klug et al. / International Journal of Cardiology 118 (2007) 249–252

MRS measurements were performed using the same MR scanner, following a protocol previously published by our study group [3]. 3. Results 3.1. Baseline Cine-MRI long-axis four-chamber view showed the typical picture of apical ballooning in both cases. Firstpass of Gd showed no pathological patterns while LEsequences demonstrated weak diffuse enhancement of all myocardial regions. MRS scan on day 1 revealed decreased PCr/b-ATP ratios in both patients (Table 1). 3.2. Follow-up CMR on follow-up showed improvement in left ventricular function as well as decreased LE. On day 9 PCr/b-ATP ratios increased by 68% in patient 1. Findings of CMR/MRS in patient 2 were similar. PCr/b-ATP ratios increased by 39% between day 1 and day 5 (Table 1). 4. Discussion Our patients clearly showed impairment of left ventricular function in long- and short-axis cine sequences. Furthermore regional SWT analysis provided highly reproducible quantification of affected apical segments in contrast to basal segments. First-pass CE-CMR studies are primarily used if acute myocardial ischemia is suspected [6]. Perfusion deficits impose as dark, Gd-hypoenhanced areas. In combination with CAG results, perfusion deficits as a cause for apical akinesia in our patients could be ruled out. Acute myocardial damage can cause diffuse hyperenhancement in LE-CMR [7]. In the study of Sharkey et al. only 1 out of 22 patients with transient apical ballooning showed LE [8]. In our study the results of patients 1 and 2 are in accordance with those findings. Moreover we detected decreased PCr/b-ATP ratios at admission and a significant increase of myocardial PCr/bATP ratios after approximately 1 week by 68% and 34%, respectively. EF improved by 46% and 29%. Myocardial PCr/ATP ratios have been recently correlated to left ventricular EF in heart failure [9] and drug treatment has been shown to be able to improve PCr/ATP ratios in those patients [5]. Whether changes in PCr/ATP ratios are a cause or a consequence of left ventricular function in our study group deserves closer investigation [10]. Stunned myocardium as a cause for transient apical ballooning is controversially discussed [11,12]. Since one report of Kalil-Filho et al. [13] ruled out stunned myocardium as a cause of decreased PCr/b-ATP ratios in reperfused myocardium we cannot consider stunned myocardium as a cause for the observations in our study population.

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Abe et al. observed reduced technetium-99m tetrofosmin uptake in almost all examined patients. Since in this study perfusion deficits due to stenosis, microvascular impairment and multiple coronary spasms were carefully ruled out, they concluded that scintigraphic abnormalities might be due to the inability of mitochondria to take up the tracer [14]. Reports on scintigraphic follow-up studies describe increased tracer uptake in the subacute phase (2–14 days) compared to the acute phase (day 1) and normal tracer uptake after a follow-up of at least 1 month [15]. Transient mitochondrial abnormalities could therefore be considered as a possible cause for our results. 5. Conclusion We are the first who detected decreased myocardial PCr/ b-ATP ratios during the first week of transient apical ballooning. After 1 week we observed an improvement of PCr/b-ATP ratios, associated with an increase in left ventricular function. So we conclude that 31P MRS might be a valuable tool in the evaluation and follow-up of apical ballooning, but larger cohorts are needed to improve the understanding of metabolic changes during transient apical ballooning. References [1] Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med Dec 7 2004;141 (11):858–65. [2] Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med Nov 16 2000;343(20):1445–53. [3] Schocke MF, Metzler B, Wolf C, et al. Impact of aging on cardiac highenergy phosphate metabolism determined by phosphorus-31 2dimensional chemical shift imaging (31P 2D CSI). Magn Reson Imaging Jun 2003;21(5):553–9. [4] Weiss RG, Bottomley PA, Hardy CJ, et al. Regional myocardial metabolism of high-energy phosphates during isometric exercise in patients with coronary artery disease. N Engl J Med Dec 6 1990;323 (23):1593–600. [5] Neubauer S, Krahe T, Schindler R, et al. 31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure. Circulation Dec 1992;86(6):1810–8. [6] Al-Saadi N, Nagel E, Gross M, et al. Noninvasive detection of myocardial ischemia from perfusion reserve based on cardiovascular magnetic resonance. Circulation Mar 28 2000;101(12):1379–83. [7] Mahrholdt H, Wagner A, Judd RM, Sechtem U. Assessment of myocardial viability by cardiovascular magnetic resonance imaging. Eur Heart J Apr 2002;23(8):602–19. [8] Sharkey SW, Lesser JR, Zenovich AG, et al. Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation Feb 1 2005;111(4):472–9. [9] Hansch A, Rzanny R, Heyne JP, Leder U, Reichenbach JR, Kaiser WA. Noninvasive measurements of cardiac high-energy phosphate metabolites in dilated cardiomyopathy by using 31P spectroscopic chemical shift imaging. Eur Radiol Feb 2005;15(2):319–23. [10] Ingwall JS, Weiss RG. Is the failing heart energy starved? On using chemical energy to support cardiac function. Circ Res Jul 23 2004;95 (2):135–45.

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[11] Abe Y, Kondo M. Apical ballooning of the left ventricle: a distinct entity? Heart Sep 2003;89(9):974–6. [12] Kurisu S, Sato H, Kawagoe T, et al. Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J Mar 2002;143 (3):448–55. [13] Kalil-Filho R, de Albuquerque CP, Weiss RG, et al. Normal high energy phosphate ratios in “stunned” human myocardium. J Am Coll Cardiol Nov 1 1997;30(5):1228–32.

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