Ann Thorac Surg 2006;82:e33-e34
© 2006 The Society of Thoracic Surgeons
Case Reports
Intracoronary Infusion of Levosimendan to Treat Postpericardiotomy Heart Failure
Philippe-Primo Caimmi, MD, MSa,*,
Elena Grossini, MD, PhDb,
Claudio Molinari, MD, PhDb,
Giovanni Vacca, MDb,
Giovanni Teodori, MDa
a Department of Cardiac Surgery, Ospedale Maggiore della Carità, School of Medicine, University of East Piedmont "A. Avogadro," Novara, Italy
b Department of Experimental and Clinical Medicine, University of East Piedmont "A. Avogadro," Novara, Italy
Accepted for publication June 22, 2006.
* Address correspondence to Dr Caimmi, Department of Cardiac Surgery, Ospedale Maggiore della Carità, School of Medicine, University of East Piedmont, Baluardo M. D'Azeglio n.5, 28100 Novara, Italy. (Email: philippe.caimmi{at}med.unipmn.it).
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Abstract
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Systemic hypotension limits the intravenous use of levosimendan, particularly in coronary disease. Published reports show that the intracoronary administration of levosimendan in animal models causes an increase of coronary blood flow without systemic hypotension. In this case report, the intracoronary administration of levosimendan bolus in a 74-year-old man with postpericardiotomy heart failure elicited beneficial cardiac effects, increasing both systolic and diastolic functions and blood flow in all of the grafts. No changes of heart rate and systemic arterial blood pressure were observed.
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Introduction
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Levosimendan is a Ca2+ sensitizing drug that exerts positive inotropic effects and vasodilation. Systemic hypotension limits the intravenous use of levosimendan, particularly in coronary disease [1]. Our previous report showed that the intracoronary administration of levosimendan in the anesthetized pig causes a dose-related increase in coronary blood flow, without any concomitant changes in arterial pressure or other hemodynamic parameters [2]. Here, we report the use of intracoronary administration of levosimendan to treat a patient with very severe postpericardiotomy heart failure.
A 74-year-old man underwent four coronary artery bypass grafting consisting of a kissing vein graft (aorta to first diagonal branch to obtuse marginal branch), a single vein graft (aorta to right coronary artery), left internal thoracic artery to left anterior descending coronary artery, and mitral annular plasty. The patient presented with preoperative ischemic dilated cardiomyopathy, with an ejection fraction of 0.13.
The weaning from cardiopulmonary bypass was very difficult, and the cardiac index was not satisfactory, even at maximal doses of inotropic drugs (dobutamine, 15 µg/[kg · min]). A severe obstructive disease of both femoral arteries did not allow the patient to be supported with intraaortic balloon counterpulsation. Levosimendan, in an intracoronary 24-µg/kg bolus, was administered in a 10-minute period (body weight, 80 kg; bolus dose, 1920 µg/20 mL in 5% glucosate) by means of a 20-mL syringe connected to a catheter in which a three-way stopcock and two butterfly needles were inserted into the kissing vein graft (aorta to first diagonal branch to obtuse marginal branch) and the single vein graft (aorta to right coronary artery), respectively. The dose of drug administered corresponded to the one commonly used in a bolus administration.
Flows of all grafts and cardiac output were measured by means of Doppler flowmeter probes. Heart rate was obtained from the electrocardiogram. Left ventricle diastolic and systolic function, given by transmitral diastolic early-to-late filling ratio (E/A) and ejection fraction, respectively, was obtained from echocardiography. Catheters were used to measure systolic and diastolic blood pressure, pulmonary systolic arterial pressure, and pulmonary wedge pressure. All measurements were performed before and after bolus administration.
At the end of the bolus administration, the effects of levosimendan on systolic arterial blood pressure, pulmonary systolic arterial pressure, and pulmonary wedge pressure were small; whereas, diastolic blood pressure and heart rate did not change. The E/A ratio and ejection fraction increased by about 71% and 0.53, respectively. These effects were accompanied by an increase in cardiac output of about 28%. The flows in the grafts increased by 110%, 42%, and 105%, whereas the systemic vascular resistances showed a decrease amounting to about 16%. The rough data are reported in Table 1. The dobutamine administration was gradually reduced from 15 µg/(kg · min) to 7.5 µg/(kg · min) in the first hour after the bolus administration of levosimendan.
The hemodynamic improvements observed were stable in the early postoperative period, the dobutamine administration was completely finished in the 48 hours after surgery, and the patient successfully overcame the postoperative period.
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Comment
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The newest and very promising approach to pharmacologic stimulation of cardiac contractility is the use of Ca2+ sensitizing agents, which increase the responsiveness of the myofilaments to Ca2+ [3]. Levosimendan, the first Ca2+ sensitizing agent introduced in the clinical use, has been shown to elicit positive inotropic effects and to decrease vascular resistances [4, 5].
Although its hemodynamic effects have been largely investigated [4, 5], levosimendan use is limited, particularly by the relevant decrease in systemic arterial pressure that occurs during its intravenous administration. In fact, decreasing the afterload may be useful to improve cardiac output, but it could actually be very dangerous, particularly with coronary disease. In the presence of critical coronary stenosis, the perfusion is pressure-dependent only, so that intravenous levosimendan administration can affect the regional kinesis.
The finding that the intracoronary administration of levosimendan does not cause a decrease of arterial pressure in an animal model [2] suggested that this method might be useful during cardiac ischemia or in end-stage heart failure.
The results obtained in this case report are consistent with previous experiences on animal models. In the patient of this study, the bolus administration of levosimendan (24 µg/kg) during a 10-minute period induced a significant increase in graft blood flow without altering cardiac rate and reducing arterial blood pressure. In addition to results previously observed in the pig, levosimendan caused an increase in left ventricular kinesis, cardiac output, and diastolic function. These findings are consistent with data reported in literature that suggest positive effects of levosimendan on cardiac function, particularly in the presence of a pathologic state, which was not present in the study published by Grossini and colleagues [2]. In fact, in the research performed by Jamali and collegues [6], the intracoronary administration of levosimendan in the dog in the presence of stunned myocardium elicited an increase in contractility and restored the ratio of effective to total regional work. In terms of diastolic function, the results obtained in our patient confirm the data present in literature on the effect of levosimendan on ventricular relaxation, which is not impaired by the drug [7].
In our patient, the intracoronary administration of levosimendan caused a reduction in systemic vascular resistance that was not accompanied by a decrease in arterial blood pressure. It could be argued that the positive effects on cardiac function that appear earlier than the fall in systemic vascular resistances could have balanced the systemic vascular dilation, thus avoiding the decrease in arterial blood pressure that could have impaired the myocardial regional kinesis. Indeed, the decrease in afterload could have enhanced the primary cardiac effects of levosimendan. Despite the very low output syndrome, the absence of hypotensive side effects of intracoronary levosimendan administration has allowed us to avoid the use of inotropic supports such as adrenaline. By this way, the myocardial contractility was supported in the absence of increases in the cardiac metabolic demands.
The beneficial effects of the intracoronary bolus of levosimendan were maintained in the postoperative period for 48 hours in the absence of any other levosimendan administration. This finding can be explained by the levosimendan pharmacokinetic profile. This drug has a half-life of 1 hour, but its active metabolite, OR-1896, which has similar hemodynamic effects of levosimendan, has a half-life of 80 hours; this also could explain the long-lasting cardiovascular effects observed in our patient after the levosimendan infusion [8].
In results similar to what observed in the animal model, the intracoronary infusion of levosimendan was not accompanied by any arrhythmias or changes in repolarization. The present case report supplies important elements to develop new protocols for levosimendan administration in cardiac surgery. The intracoronary administration of levosimendan results in favorable cardiac anti-stunning effects without lowering systemic arterial pressure. These properties are particularly appreciable during reperfusion of the heart after cardioplegic arrest.
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References
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- Pieske B. Levosimendan in regional myocardial ischemia Cardiovasc Drugs Ther 2002;16:379-381.[Medline]
- Grossini E, Caimmi PP, Molinari C, Teodori G, Vacca G. Hemodynamic effect of intracoronary administration of levosimendan in the anesthetized pig J Cardiovasc Pharmacol 2005;46:333-342.[Medline]
- Ver Donck J. Calcium-sensitizing drugs: positive inotropy by enhanced sensitivity of the contractile apparatus to calcium Cardiovasc Drugs Rev 1996;14:185-212.
- Figgitt DP, Gillies PS, Goa KL. Levosimendan Drugs 2001;61:613-627.[Medline]
- Kaheinen P, Pollesello P, Levijoski J, Haikala H. Levosimendan increases diastolic coronary flow in isolated guinea-pig heart by opening the ATP-sensitive potassium channels J Cardiovasc Pharmacol 2001;37:367-374.[Medline]
- Jamali IN, Kersten JR, Pagel PS, Hettrick DA, Warltier DC. Intracoronary levosimendan enhances contractile function of stunned myocardium Anesth Analg 1997;85:23-29.[Abstract]
- Haikala H, Nissinen E, Etemadzadeh E, Levijoki J, Linden IB. Troponin C-mediated calcium sensitization induced by levosimendan does not impair relaxation J Cardiovasc Pharmacol 1995;25:794-801.[Medline]
- Kivikko M, Lehtonen L, Colucci WS. Sustained hemodynamic effects of intravenous levosimendan Circulation 2003;107:81-86.[Abstract/Free Full Text]
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Abstract
Introduction
