Ann Thorac Surg 1999;68:2177-2180
© 1999 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Myocardial recovery after mechanical support for acute myocarditis: is sustained recovery predictable?
Rémi Houël, MDa,
Emanuelle Vermes, MDa,
Denis B. Tixier, MDa,
Paul Le Besnerais, MDa,
Nicole Benhaiem-Sigaux, MDa,
Daniel Y. Loisance, MDa
a Service de Chirurgie Thoracique et Cardiovasculaire, Hopital Henri Mondor, Créteil, France
Address reprint requests to Dr Houël, Service de Chirurgie Thoracique et Cardiovasculaire, Hôpital Henri Mondor, 51, ave du Maréchal de Lattre de Tassigny, 94010 Créteil, France;
e-mail: loisance{at}univ-paris12.fr
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Abstract
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Background. At present, myocardial recovery with mechanical support for acute myocarditis is a more frequently observed issue. However, predictive parameters of a sustained myocardial recovery are still under investigation.
Methods. Two recent cases of mechanical support for acute lymphocytic myocarditis with two different outcomes are reported. Literature about this disease and predictability of a sustainable myocardial recovery are reviewed.
Results. Acute lymphocytic myocarditis is an individual entity whose outcome is associated with the importance of healed cell damage. Unfortunately, there are no available means of quantifying the fibrotic scar and endomyocardial biopsy has a high percentage of false-negative results. Echocardiographic assessment of systolic and diastolic cardiac function is difficult while under mechanical support and its significance is not obvious. Forthcoming development of Doppler could better correlate myocardial contractility and histology to be predictive of a sustained recovery after acute myocarditis under mechanical support.
Conclusions. Long-lasting recovery after mechanical support for acute myocarditis remains unpredictable in our experience. More predictive factors are needed.
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Introduction
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At present, acute myocarditis is a good indication for mechanical support as a bridge to myocardial recovery and some experience has now been gained in this field [1–7]. Predicting myocardial recovery after acute myocarditis has some implication in the selection of the optimal device and in the indication for heart transplantation. Moreover, active myocarditis may predispose patients to more frequent early severe rejection and higher mortality after heart transplantation [8]. Ejection fraction and ventricular dimensions measured by echocardiography or radionuclide scanning are the most widely used parameters for assessment of left ventricular recovery. Determining a predictive parameter of sustainable myocardial recovery would be of interest and is currently unavailable. This study reports on 2 patients with acute myocarditis, who were initially similar in many clinical aspects, but in whom evolution after a successful period of temporary biventricular support differed dramatically: a sustained ventricular recovery in one, and a rapid deterioration, fortunately stopped by a lifesaving heart transplantation in the other. We have reviewed and discussed the literature in this perspective.
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Patients and methods
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Patient 1
A 17-year-old woman with no medical history was admitted with acute dyspnea after a 1-week history of flu-like symptoms. On admission, there were some signs of right ventricular failure on physical examination but a radionuclide perfusion scan failed to show any lung defect characteristic of pulmonary embolism. She rapidly deteriorated and required intubation. The echocardiogram showed a normal left ventricular size but a severe global hypokinesia (ejection fraction was measured at 9% using the Simpson methods). Right ventricle was dilated and akinetic. Inotropic support with dobutamine was commenced, mean arterial pressure was 70 mm Hg, pulmonary wedge pressure 14 mm Hg, central venous pressure 12 mm Hg with a cardiac index of 1.6 L · min-1 · m-2 and a sinus heart rate at 160 beats/min. Diuresis was maintained and she had no liver failure. Despite optimization of pharmacologic support (under increment doses of dobutamine and dopamine) and fluid replacement, there was no improvement and she underwent implantation of a biventricular external assist device (Thoratec Inc, Berkeley, CA). Histology from specimens taken during operation showed an acute myocarditis with lymphocytic infiltration, interstitial edema, and large foci of recent necrosis (Fig 1). Immunosuppressive therapy was commenced using high doses of steroids (prednisolone 1 g/day for 3 days). On the fourth postoperative day, there was some evidence of myocardial recovery on the transesophageal echocardiogram (TEE device on): shortening fraction (transgastric view, 0°, short axis) measured was 38% and right ventricular function had improved. She was weaned from right ventricle support on the 10th postoperative day. Ten days later, the device was set to an asynchronous mode with a rate of 50 beats/min and she was treated with angiotensin-converting enzyme inhibitors (ramipril, 2.5 mg/day) for 5 days. Back in the operating room the device was turned off for 5 minutes and then off for 15 minutes (maintained off). Transesophageal echocardiography showed sustained good left ventricular kinetics with a shortening fraction of 45% (transgastric view, 0°, short axis). The device was explanted on the 12th postoperative day. Subsequent transthoracic echocardiography showed a continuous recovery of the right and left ventricles, which was confirmed by radionuclide scanning (right ejection fraction of 56% and left ejection fraction of 50%). The patient was back home 2 months later with a normal exercise tolerance. No further endomyocardial biopsy was proposed.
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Fig 1. Photomicrograph of histologic specimen (hematoxylin and eosin stain, x250 magnification) in patient 1 showing a major edematous reaction dissociating myocytes associated with mononuclear cell infiltration. This specimen was taken at the time of mechanical support implantation.
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Patient 2
The patient was a 49-year-old woman with a past medical history of pericarditis 2 years previously, which had completely resolved. She was admitted to her local hospital with dyspnea, fatigue, and fever after a 4-day history of flu-like symptoms. On admission, she was in cardiogenic shock. Angiography failed to demonstrate coronary artery disease. Myocardial biopsy was performed on the right ventricle, which showed acute myocarditis with recent necrosis, lymphocytic, and numerous polynuclear neutrophil infiltration. The transthoracic echocardiogram showed both left and right ventricles to be hypokinetic with a normal-sized heart and a small pericardial effusion. Mean arterial pressure was 69 mm Hg, pulmonary wedge pressure was 18 mm Hg, and central venous pressure 15 mm Hg with a cardiac index of 1.8 L · min-1 · m-2 in sinus tachycardia at 150 beats/min with inotropic support using dobutamine and dopamine. She rapidly deteriorated, was intubated, and referred to our center in severe cardiogenic shock with oliguria but no liver dysfunction despite hepatic cytolysis (bilirubinemia, 17 mmol/L; prothrombin time, 60%; factor V, 45%). Immediately, she was brought to the operating room for a rescue implantation of a biventricular external assist device (Thoratec Inc). She eventually recovered despite a period of 3 weeks on hemodialysis. Histology from a specimen of myocardium harvested from the left ventricular apex at the time of the implantation confirmed an acute myocarditis with lymphocytic infiltration, no interstitial edema, and no coexisting healed cell damage (fibrosis) (Fig 2). On the 14th postoperative day, she was brought back to the operating room for cardiac tamponade. Intraoperatively, TEE confirmed recovery of the right ventricular function that allowed her to be weaned off the right ventricular assist device. Left ventricular function had also improved on echocardiographic assessment with a shortening fraction of 32% (transgastric view, 0°, short axis). During the following days, the left ventricle showed a progressive recovery despite an episode of infection. After 2 months on left ventricular support, the left ventricular function was assessed using TEE, device turned off, after 5 days pumping in an asynchronous mode at a rate of 45 beats/min and administration of angiotensin-converting enzyme inhibitors (ramipril, 2.5 mg/day). AntiIIa factor activity was 0.3 UI/L under heparin infusion. The echocardiography (transgastric view, 0°, short axis) showed a sustained ejection fraction of 32% with a velocity/time integral of 16 cm, and arterial pressure was 125/70 mm Hg and in sinus heart rate at 110 beats/min. On the 50th postoperative day, she was returned to the operating theater for device explantation. The echocardiographic measurements confirmed ventricular function recovery after 5 and then 15 minutes, device being off (telediastolic diameter, 40 mm; shortening fraction, 30%; velocity/time integral, 12 cm; arterial pressure, 110/60 mm Hg; sinus heart rate, 110 beats/min at 15 minutes after the device was turned off). She was then weaned off the left ventricular assist device and brought back to the intensive care unit with stable hemodynamics. Two hours later, she progressively deteriorated and rapidly necessitated an inotropic support. The TEE confirmed a severe left and right ventricular dysfunction. Fortunately, an unexpected heart donor was located and she underwent heart transplantation 20 hours after the left-assist device explantation. Histology of the native heart showed numerous foci of healed cell damage with extensive fibrosis and some persistent lymphocytic infiltrates and a few foci of cell damage (Fig 3). Two months later, this patient is back home after only one episode of rejection (class IIa), which resolved after three doses of prednisolone.
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Fig 2. Photomicrograph of histologic specimen (hematoxylin and eosin stain, x100 magnification) in patient 2 showing large area of polymorphonuclear leukocyte infiltration with areas of recent acidophilic necrosis of myocytes. This specimen was taken at the time of mechanical support implantation.
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Fig 3. Photomicrograph of histologic specimen (Masson trichrome stain, x25 magnification) showing large area of fibrous reaction with mononuclear cell interstitial infiltration in place of extensive myocyte necrosis in patient 2. This specimen was taken at the time of explantation of the native heart for transplantation.
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Comment
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Many aspects of acute myocarditis remain poorly understood and these uncertainties make therapeutic strategies extremely difficult. This is reflected by the nomenclature of many different pathologic conditions using the same name [9–11]. Fenoglio and colleagues [11] have proposed a classification for myocarditis based on clinical and pathologic findings in a group of 34 patients. They considered acute, rapidly progressive, and chronic myocarditis as separate entities. Acute myocarditis was characterized by a clinical history of viral-like syndrome at the onset associated with a rapid development of cardiac failure. At histology, this entity is characterized by marked foci of cell damage with no resolution or healed cell damage such as fibrosis. Later in the course of acute myocarditis, the pathology is characterized by scattered fibrosis with no further evidence of active cell damage. This description could well correlate with our 2 patients, which we would classify as suffering from acute myocarditis. According to Fenoglio and associates [11], patients with acute myocarditis die within a few weeks or recover nearly completely within weeks, in contrast to rapidly progressive myocarditis and chronic myocarditis. In these latter conditions, pathologic findings are predominantly characterized by foci of healing or fibrosis with cell damage coexisting with a persisting inflammatory infiltrate in chronic myocarditis. It appears that one cannot expect the same degree of recovery from these different conditions.
It must be emphasized that the histologic diagnosis is difficult and false-negative reports can be as high as 55% despite five samples taken from the right side of the heart by endomyocardial biopsy [10, 12]. Lymphocytic myocarditis may be heterogeneously distributed within the myocardium, can be localized to the epicardium, or may be deep within the septum [11, 13, 14].
Temporary mechanical support is conceptually the optimal treatment in patients deteriorating rapidly. It allows survival, control and recovery of organ dysfunction, gaining time to permit, if possible, myocardial recovery, and healing of the myocardial process. Reviewing the literature since 1988, to our knowledge, there are only 9 adult patients sustained with mechanical support for acute myocarditis in adults [1–7]. Ages range from 19 to 40 years, with a mean of 30.5 years. All patients presented with a history of flu-like symptoms in an otherwise healthy person. None had dilated cardiomyopathy and onset of cardiac failure was fulminant leading to cardiogenic shock within a few days (mean, 5.3 days). All patients had an external mechanical device implanted; 5 received biventricular support, 4 received a left ventricular assist device. Mean duration of the support was 20 days (range, 3 to 70 days).
Jett and colleagues [7] proposed a close correlation between the disappearance of the cellular infiltrate and the improvement of systolic function in lymphocytic acute myocarditis. In our experience, in patient 2, we did not find this correlation. A significant improvement was documented after nearly 3 months of support in this patient, which led us to believe that recovery would sustain. However, this patient had to be transplanted 20 hours after removal of the device for an evolving cardiogenic shock. On the explanted native heart, pathologic findings showed numerous foci of healed cell damage with significant lymphocytic infiltrate. In our opinion, the importance of the scars of fibrotic tissue might be a more valuable histologic marker of sustainable recovery after mechanical support rather than the importance of an inflammatory infiltrate. Moreover, the time lapse of apparent recovery between the weaning procedure and the further deterioration could be partly related to the load-dependent improvement in ventricular function brought out by 2 months of support. Our hypothesis is supported by Levin and associates [15], who reported a case of rapidly progressive myocarditis. This transient normalization of systolic and diastolic function after a long period of support through improvement of load-dependent dysfunction of the failing heart has implications in the application of a mechanical bridge to recovery, which are beyond the scope of acute myocarditis [16–20].
Acute myocarditis is a model of recovery after mechanical assist device implantation, but there is still no measurable parameter available that would be predictive of a sustainable recovery after mechanical support. Most of the reports used the ejection fraction assessed by radionuclide scan or echocardiography to document the improvement of ventricular dysfunction. However, it is not clear whether these measurements were done with the device turned off or on. In our experience (with patient 2), the initial normalized left ventricular function measured by TEE might have corresponded to the effect of chronic unloading on the left ventricle and not to a true recovery. Left ventricular function as assess by TEE using shortening fraction or calculated ejection fraction and velocity/time integral might not be a sufficient parameter to predict sustained recovery after acute myocarditis. In dilated cardiomyopathy, some investigators experienced a sustained recovery after several months of support [19, 21]. Westaby and colleagues [21] used M-mode and Doppler echocardiography to measure left ventricular minor axis dimensions and flow velocity at the tip of the mitral valve, respectively, at 4, 6, and 8 weeks after implantation of a left ventricular assist device. They documented an improved flow pattern through the mitral valve corresponding to an improved diastolic function concomitant on improved systolic function. Loebe and associates [22] used hemodynamics measurements up to 40 minutes after the left ventricular assist device was turned off to predict a sustained recovery. Müller and colleagues [17] hypothesized that a decrease in anti-ß-adrenoreceptors could predict a persistent recovery. Their measurements were in parallel with a decrease in plasmatic norepinephrine and cytokines levels that had been documented by Goldstein and associates [23] in patients undergoing mechanical support. Whether these measurements correspond to the improved load-dependent ventricular dysfunction or to a sustained myocardial recovery remains to be confirmed for this index to be predictive of long-lasting myocardial recovery.
Myocardial contractility could be assessed by echocardiography and Doppler, unfortunately however, the index used are load-dependant measures and unreliable in circumstances of mechanical support. Development of Doppler tissue imaging might be of some help in the future to correlate regional myocardial contractility to the degree of myocardial fibrosis or infiltration by inflammatory cells to be predictive of recovery [24].
In conclusion, myocardial recovery in patients undergoing mechanical support for acute myocarditis remains difficult to predict despite improvements in parameters of diastolic and systolic function. The 2 patients in this study suggest that a more precise histologic evaluation of myocardial damage could play a role in the prediction of a sustained myocardial recovery in acute myocarditis. An echo-Doppler index with a closer correlation between histology and assessment of cardiac function remains to be developed in this perspective.
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References
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Accepted for publication May 14, 1999.
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Abstract
Introduction
