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European Journal of Heart Failure 2007 9(9):897-900; doi:10.1016/j.ejheart.2007.05.003
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© 2007 European Society of Cardiology

Levosimendan allows detection of contractile reserve in patients with chronic ischaemic left ventricular dysfunction and non-diagnostic dobutamine echocardiography

Cinzia Cianfroccaa,b,*, Francesco Pellicciaa,b, Antonio Auritia, Vincenzo Guidoa, Vincenzo Pasceria, Xue Lia, Giuseppe Richichia, Giuseppe Mercurob and Massimo Santinia

a Department of Cardiology, San Filippo Neri Hospital Rome, Italy
b Department of Cardiovascular and Neurological Diseases, University of Cagliari Cagliari, Italy

* Corresponding author. Viale Liegi 49, 00198 Rome, Italy. Tel.: +39 347 3437648; fax: +39 06 330 62516. E-mail address: c.cianfrocca{at}mclink.it


   Abstract
Top
 Abstract
1. Background and aim
 2. Methods
 3. Results
 4. Conclusion
 References
 
Background: Dobutamine echocardiography is commonly used to detect contractile reserve in ischaemic left ventricular (LV) systolic dysfunction, although its sensitivity and specificity are not optimal. We tested the hypothesis that echocardiography with levosimendan could identify contractile reserve in patients with a non-diagnostic dobutamine test.

Methods: Twenty-two patients with LV ejection fraction <40% and non-diagnostic dobutamine echocardiography underwent levosimendan challenge (24 µg/kg in 10 min) prior to coronary angioplasty or surgery.

Results: Contractile reserve was identified by levosimendan in 10 patients (Gr. A) but was not seen in 12 patients (Gr. B). With levosimendan, LV ejection fraction increased and wall motion score index decreased significantly in Gr. A, but only slightly in Gr. B. Similarly, mean mitral annular plane excursion and peak systolic mitral annular motion velocity increased significantly in Gr. A only. Six months after revascularisation, contractile reserve was seen in 8/10 Gr. A patients but in only 2/12 Gr. B patients (80= vs 17=, p=0.011). LV ejection fraction, wall motion score index, mean mitral annular plane excursion and peak systolic mitral annular motion velocity were significantly higher in Gr. A than in Gr. B.

Conclusion: Levosimendan echocardiography can identify contractile reserve in a sizeable proportion of patients with chronic ischaemic LV dysfunction and a non-diagnostic dobutamine test.

Key Words: Contractile reserve • Echocardiography • Levosimendan • Revascularisation

Received March 5, 2007; Accepted May 3, 2007


   1. Background and aim
Top
 Abstract
 1. Background and aim
2. Methods
 3. Results
 4. Conclusion
 References
 
Detection of contractile reserve in patients with ischaemic left ventricular (LV) dysfunction has important prognostic and therapeutic implications [1,2]. To this end, dobutamine echocardiography has become the most widely used test because it has a good predictive value for functional recovery after revascularisation [3,4]. Sensitivity and specificity of the test, however, are sometimes reduced by induction of myocardial ischaemia and by the occurrence of side effects during drug infusion [5,6].

We tested the hypothesis that echocardiography with levosimendan, a new inotropic drug used successfully for acute treatment of advanced heart failure [7], could identify contractile reserve in patients with chronic ischaemic LV dysfunction that have non-diagnostic findings with dobutamine.


   2. Methods
Top
 Abstract
 1. Background and aim
 2. Methods
3. Results
 4. Conclusion
 References
 
Between January 2003 and December 2004, 443 patients with chronic ischaemic disease and a LV ejection fraction <40% had dobutamine echocardiography (low-high dose protocol) at our laboratory to assess contractile reserve [8]. Non-diagnostic findings with dobutamine were seen in 22 patients (17 men, aged 65±8 years) because of occurrence of arrhythmias (9 cases), intolerance to the drug (3 cases), equivocal results (5 cases), and unclear biphasic responses (5 cases). These patients underwent levosimendan challenge prior to percutaneous coronary revascularisation or coronary artery bypass grafting. Infusion of levosimendan diluted with saline at a concentration of 2.25 µg/mL, at 24 µg/kg over 10 min [7,9] was completed in all patients. The only side effects reported with levosimendan were headache (one case) and asymptomatic hypotension (one case with blood pressure <90 mm Hg).

Standard Doppler echocardiography and pulsed tissue Doppler were performed using the Vivid 7 system equipped with tissue Doppler capabilities (General Electric, Horten, Norway). LV ejection fraction, wall motion score index, mitral annular plane systolic excursion [10], and systolic mitral annular motion velocity [11,12] were evaluated as indices of LV systolic function. Contractile reserve was diagnosed if global LV ejection fraction improved by >10% on stress echocardiography, as compared with baseline values [13-15]. Segments were considered viable if they showed an improvement ≥1 point in the wall motion score index during stress echocardiography without further worsening [16,17]. A delta in wall motion score index ≥0.40 [17], and an improvement in ≥25% of severely dysfunctional segments [18] were evaluated as measures of viability.


   3. Results
Top
 Abstract
 1. Background and aim
 2. Methods
 3. Results
4. Conclusion
 References
 
Contractile reserve was identified by levosimendan in 10 patients (Gr. A) but was not seen in the remaining 12 patients (Gr. B) (Fig. 1). The two groups did not show any significant differences in clinical, echocardiographic and angiographic features at baseline (Table 1).


Figure 01
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  		Fig. 1 Changes in left ventricular ejection fraction during levosimendan infusion and at 6-month follow-up echocardiography for patients in Gr. A ({blacktriangleup}) and Gr. B ({circ}).

 


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  		Table 1 Presenting features, procedural characteristics, and medical treatment in the two groups of patients

 
After levosimendan (Table 2), LV ejection fraction increased and wall motion score index decreased significantly in Gr. A, but only slightly in Gr. B. Mean mitral annular plane excursion and peak systolic mitral annular motion velocity increased in Gr. A but not in Gr. B. Also, a change in wall motion score index ≥0.40 or an improvement in ≥25% of severely dysfunctional segments was seen in the majority of Gr. A patients; but in only one of the Gr. B patients.


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  		Table 2 Echocardiographic findings at baseline, after levosimendan, and at 6-month examination

 
All patients underwent successful coronary revascularisation by either percutaneous coronary intervention (n=17) or by-pass surgery (n=5).

At 6-month follow-up, echocardiography showed a significant improvement of indices of LV systolic function compared with baseline in Gr. A but not in Gr. B (Table 2). Contractile reserve was seen in 8/10 Gr. A patients and in 2/12 Gr. B patients (80% vs 17%, p=0.011)(Fig. 1). LV ejection fraction, wall motion score, mean mitral annular plane excursion and peak systolic mitral annular motion velocity became significantly different between Gr. A and Gr. B at variance with baseline. A change in wall motion score index ≥0.40 or an improvement in ≥25% of severely dysfunctional segments was seen in the majority of Gr. A patients, but in only 2 and 3 Gr. B patients, respectively.


   4. Conclusion
Top
 Abstract
 1. Background and aim
 2. Methods
 3. Results
 4. Conclusion
References
 
Our results suggest that levosimendan challenge can effectively predict recovery of LV systolic function after revascularisation in a sizeable proportion of those patients who have a non-diagnostic dobutamine echocardiography test.

Levosimendan is a calcium sensitizer, a new inotropic drug that acts directly on contractile proteins without increasing intracellular calcium [7]. Thus, it may enhance myocardial function without increasing myocardial oxygen consumption or inducing arrhythmias [7]. Due to its novel mechanism of action, levosimendan does not share the pro-arrhythmic and pro-ischaemic effect of dobutamine and therefore we reasoned that the drug could be an optimal pharmacological tool for detection of contractile reserve in patients with LV dysfunction of ischaemic origin.

Our results support this hypothesis, as levosimendan could be used without significant side effects in those patients that had dobutamine infusion stopped because of ventricular arrhythmias. Also, levosimendan was effective in detecting contractile reserve even in the proportion of patients with ischaemic LV dysfunction who had no clear evidence of contractile reserve with dobutamine. Our results are in keeping with a recent study which showed that a 10-minute infusion of 24 µg/kg of levosimendan induced a significant improvement of contractility in stunned myocardium measured 20 min after the end of the infusion [9]. A clinical implication from our trial is that revascularisation may be beneficial in some patients not responding to dobutamine, but our findings need confirmation in a larger study.


   Acknowledgements
 
We thank Filomena Agostini, RT, for her technical help and Cinzia Bossi, RN, Mascia Valentini, RN, Paola Serafini, RN, and Pino Scisciolo, RN, for their support.


   References
Top
 Abstract
 1. Background and aim
 2. Methods
 3. Results
 4. Conclusion
 References
 

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  18. Sicari R., Picano E., Cortigiani L., et al. Prognostic value of myocardial viability recognized by low-dose dobutamine echocardiography in chronic ischemic left ventricular dysfunction. Am J Cardiol (2003) 92:1263–1266.[CrossRef][Web of Science][Medline]

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This Article
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