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Ann Thorac Surg 1995;60:392-397
© 1995 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Left Ventricular Assistance With the Transthoracic 24F Hemopump for Recovery of the Failing Heart

Department of Cardiac Surgery, Gasthuisberg University Hospital, Leuven, Belgium

Accepted for publication April 4, 1995.

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Background. The Hemopump was developed as a more powerful assist device for postcardiotomy support in patients in whom the intraaortic balloon pump is insufficient.

Methods. Over a 2-year period 21 (0.8%) of 2,585 patients undergoing cardiac operations needed a ventricular assist device because of postcardiotomy heart failure unresponsive to pharmacologic and intraaortic balloon support. Sixteen of these patients were assisted with the 24F transthoracic Hemopump left ventricular assist device. The aim of the mechanical support was myocardial recovery as the underlying conditions (age, arterial hypertension, diabetes, vascular and pulmonary disease) excluded heart transplantation.

Results. Hemodynamic improvement was apparent with a decrease in left atrial pressure (mean, 18.6 to 9.2 mm Hg), an increase in arterial blood pressure (mean, 54.1 to 70.1 mm Hg), and an increase in cardiac index. Five patients died within the first 24 hours because of low cardiac output. Although the heart was well unloaded (decrease in left atrial pressure of 8 ± 4.69 mm Hg versus 9.3 ± 5.51 mm Hg for the other patients), the increase in cardiac index was significantly lower (+0.516 versus +1.377 L • min^-1 • m^-2; p = 0.027). Three of these 5 patients were known to have severe left ventricular hypertrophy. Of the remaining 11 patients, 2 were assisted for 1 week but failed to show recovery of the myocardium, 8 (50%) were weaned, and 4 (25%) were discharged. There were no device-related complications except the thrombosis of a cannula that was left for 10 days.

Conclusions. The transthoracic Hemopump is an easy-to-use and reliable assist device. Left ventricular hypertrophy is a relative contraindication for the use of the Hemopump.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Left ventricular failure is the most frequent cause of death in cardiac surgery [1]. The intraaortic balloon pump (IABP) often is used in postcardiotomy heart failure because it reduces ventricular afterload, enhances subendocardial perfusion, and improves survival [2]. However, cardiac output is only increased by 10% to 15%, and mortality is still high in this group of patients [3]. Two basic tools to increase survival are (1) assisting the high-risk patients earlier and (2) assisting with more powerful devices.

The increasing age of the operated population and the complexity of their pathology generates more indications for more powerful left ventricular assistance. Many of these patients are excluded from heart transplantation because of underlying conditions such as diabetes, chronic pulmonary disease, peripheral vascular disease, and age. In these patients temporary cardiac assistance to overcome the stunning period of the myocardium is the only chance of survival. In the last 2 years we have used the transthoracic 24F Hemopump (Johnson & Johnson Interventional Systems, Rancho Cordova, CA) as a more powerful assist device in those patients in whom the IABP pump was not sufficient to overcome the low cardiac output state. Here we report our experience with this device.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Patients
From January 1, 1993, through December 31, 1994, 2,585 patients underwent cardiac operations in the Gasthuisberg University Hospital in Leuven, Belgium. In 96 patients (3.71%) an IABP was inserted, and in 21 patients (0.8%) a more powerful assist device was needed to restore sufficient organ perfusion. This more powerful assist device was in 5 cases the Abiomed BVS 5000 (Abiomed Inc, Danvers, MA) assist device for right and biventricular support and in 16 patients the 24F Hemopump transthoracic left ventricular assist device. Use of the Hemopump device was approved by the institutional review board, and consent was obtained from each patient or his or her family in cases of unconsciousness.

Table 1 lists the biographic data of these 16 patients. Mean age was 65.5 years (range, 54 to 76 years). There were 7 female and 9 male patients. Patients were considered in low cardiac output due to left ventricular failure if the cardiac index was less than 2 L • min^-1 • m^-2 or systolic arterial blood pressure was less than 90 mm Hg with left atrial pressure greater than 20 mm Hg despite maximal pharmacologic support and IABP use. Six patients were unweanable from the extracorporeal circulation and had their Hemopump inserted in the operating room. Ten initially were weaned but had low cardiac output syndrome later. In 2 patients (patients 3 and 14) the attempts to improve the patient's condition by pharmacologic support and IABP have taken so much time that these patients were 10 and 28 hours in low cardiac output before the Hemopump was started.

Seven patients were operated on urgently, this because of ischemia without shock (2 patients) or ischemia with shock (5 patients of whom 4 needed cardiopulmonary resuscitation before operation). Four of these urgent cases were failed percutaneous transluminal coronary angioplasty procedures. In addition, 2 patients needed cardiopulmonary rescucitation in the postcardiotomy period before Hemopump insertion. In 4 patients, the insertion of an IABP was technically impossible because of peripheral vascular disease (aorto–bifemoral bypass in 3 and bilateral iliac artery occlusion in 1 patient).

In all these patients the primary goal was recovery of the myocardium, and most of them were excluded from heart transplantation because of the underlying conditions.

Transthoracic Hemopump
The Hemopump is a catheter-mounted axial-flow pump expelling blood from the left ventricular cavity into the ascending aorta. Therefore it needs to be positioned through the aortic valve. Due to the shorter inflow tip and the better design of the rotator, the transthoracic 24F cannula performs better than the cannula that was developed for introduction through the groin. The transthoracic Hemopump produces in vitro, at a maximum speed of 26,000 revolutions per minute and with a pressure difference of 70 mm Hg, a nonpulsatile flow of 4.8 L/min. The cannula length is 8.5 cm, and the maximum diameter is 8.1 mm (24F). In this series, only the transthoracic 24F cannula was used.

Surgical Technique
A 12-mm Dacron graft is sutured on the ascending aorta, and the Hemopump cannula is introduced through the graft. The position of the cannula is confirmed by direct palpation of the ascending aorta. The occluding plugs around the drive cable are tied to prevent blood loss through the graft and to secure the cannula in its position (Fig 1). This procedure requires no cardiopulmonary bypass support. The right pleural space is opened and the drive cable is positioned in a smooth curve on top of the right lung, leaving the chest at the caudal end of the sternotomy. If tolerated the sternum is closed with steel wires. Resternotomy is required to remove the cannula. During removal, the graft is clamped as low as possible and sutured.

View larger version (38K): [in this window] [in a new window]   Fig 1. . Position of the 24F Hemopump in the left ventricular cavity (A) and in the mediastinum (B).

Mechanical ventilation and sedation were continued for the entire assist period. Hemodynamic goals were a mean arterial pressure of 70 to 90 mm Hg, a left atrial pressure of 10 to 15 mm Hg, and a central venous pressure of 10 to 15 mm Hg. The central venous pressure was considered the critical value for regulation of the fluid balance. As no Hemopump flow is displayed, we have to rely on indirect measurements of this flow. Cardiac output measurement by thermodilution is an estimation of the combined outputs of the left ventricle and the Hemopump cannula. It therefore gives a good idea of the delivered flow to the peripheral organs.

Left ventricular function was judged on transesophageal echocardiography before removal of the pump. In cases where an IABP was present, this IABP was left in place. The IABP generates a pulsatile pressure wave with diastolic pressures higher than systolic pressures. We continued the counterpulsation even after the removal of the Hemopump as support for the first postweaning days.

Statistics
Continuous data are presented with their standard deviation. Paired data are analyzed with the Wilcoxon signed rank test, unpaired data with the Mann-Whitney U test.

	Results

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Hemodynamic Recovery and Survival
In all patients immediate hemodynamic improvement was found by an immediate decrease in left atrial pressure, increase in mean arterial blood pressure, and increase in the cardiac index. Mean left atrial pressure decreased from 18.6 ± 4.4 to 9.2 ± 3.5 mm Hg (p = 0.0015). The mean arterial blood pressure increased from 54.1 ± 10.9 to 70.1 ± 10.1 mm Hg (p = 0.0033). The overall evolution of the cardiac index is depicted in Figure 2.

View larger version (13K): [in this window] [in a new window]   Fig 2. . Evolution of cardiac index (±standard deviation) during Hemopump support.

View larger version (17K): [in this window] [in a new window]   Fig 3. . Lactate levels (±standard deviation) during Hemopump assist.

Duration of support, outcome, and complications are listed in Table 2. There was no significant difference in outcome in patients assisted with the Hemopump and the IABP (n = 12) and those patients assisted with the Hemopump alone (n = 4).

PATIENTS WHO DIED WITHIN 24 hours.
In 5 patients the immediate hemodynamic recovery was only moderate. In these patients left ventricular unloading was present (mean decrease in left atrial pressure, 8 ± 4.69 mm Hg) and comparable with the left atrial pressure drop in the other 11 patients (mean decrease in left atrial pressure, 9.3 ± 5.51 mm Hg; p > 0.05). However Hemopump support was not sufficient as the increase in mean arterial blood pressure was significantly less pronounced (mean 0.75 ± 4.35 versus 20.8 ± 16.54 mm Hg; p = 0.0109) and the increase in cardiac index was significantly less (+0.516 versus + 1.377 L • min^-1 • m ^-2; p = 0.0275). Even more striking is the difference in highest cardiac index reached within the first 12 hours (mean, 2.1 ± 0.477 versus 3.3 ± 0.729 L • min^-1 • m^-2; p = 0.0027). As a matter of fact, all patients with a cardiac index less than 2.5 L • min^-1 • m^-2 after 12 hours of hemopump assistance died within the first day. the preassist factors duration of shock and cardiopulmonary rescucitation were not different for these patients compared with the better assisted patients (see table 1). inotropic support could not be reduced in these patients.

In 1 patient (patient 3) the Hemopump assistance led immediately to an increasing central venous pressure with low pulmonary pressures, and the hemodynamic diagnosis of right ventricular failure became obvious after left ventricular assistance. The diagnosis was confirmed by the finding of a dilated, hardly contracting right ventricle on transesophageal echocardiography. It was decided, however, that further invasive therapy was useless because of the poor general state of the patient and therefore no biventricular assist was initiated. In the other 4 patients decreasing peripheral vascular resistance led to decreasing arterial blood pressure with death, by arrhythmia, as a consequence. Interestingly, 3 of these patients were known to have long-standing arterial hypertension and left ventricular hypertrophy. In these cases the inflow of the Hemopump was reduced. None of these failures was due to a technical problem as all the removed cannulas were tested and approved.

PATIENTS WHO SURVIVED THE FIRST 24 hours.
Of the 11 patients with sufficient support 8 were weaned (50% of the total) and 4 were discharged home (total hospital mortality, 75%).

Inotropic support, expressed as combined micrograms per kilogram body weight per minute of dopamine and dobutamine, was reduced from 15.1 ± 8.7 in the preassist state to 6.1 ± 4.6 after 2 days of assisting (p = 0.0009).

Two patients were supported for 7 days in a perfect hemodynamic state but died because the left ventricle did not recover (patients 5 and 15). One patient died the third day of support due to untreatable ventricular arrhythmia.

Of the 8 weaned patients, 4 died. Causes of death all were related somehow to the low cardiac output state these patients had gone through (hepatic failure, necrotic cholecystitis, multiple organ failure, and adult respiratory distress syndrome).

Complications
There were 2 cases of hemolysis (plasma free hemoglobin level >40 mg/dL). In both cases this laboratory finding was transient and had no clinical consequences.

Bleeding complication, defined as blood loss exceeding 1,500 mL in 12 hours or revision, occurred in 4 cases: 1 revision and 3 excessive bleeders. One cannula thrombosed, although the activated clotting time was kept between 180 and 200 seconds. This patient failed to recover, and after 7 days there was still no sign of left ventricular performance. More invasive therapy was not considered as he was not a candidate for heart transplantation. Pumping was continued and the Hemopump thrombosed on day 10 with death in low cardiac output as a consequence.

There were no cases of drive cable fracture, cannula displacement, or difficulties introducing or removing the cannulas. There were no cases of emboli or neurologic events.

	Comment

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Mechanical support reduces myocardial oxygen consumption and infarct size and enhances myocardial recovery after stunning (4–9). The step to prophylactic assisting is logical. However, the invasiveness and the morbidity of most of the assist devices prevents such liberal use. The less powerful femoral Hemopump cannula already has proved to be beneficial in the treatment of shock patients [10, 11]. In addition, the concept of transvalvular unloading with an axial-flow pump was tested experimentally in a canine model and proved to provide sufficient left ventricular unloading and improved myocardial blood flow in the normal as well as in the ischemic myocardium [4–6]. In addition, it was shown that the Hemopump's effect was dependent on the heart function itself and that the reduction in myocardial O₂ demand induced by the Hemopump was more pronounced when the cardiac dysfunction was severe [6]. This interaction between cardiac function and Hemopump function permits a gradual and spontaneous weaning from the assisted circulation.

The reliability and the technical ease we experienced with this transthoracic Hemopump indicates that earlier use of this device is defensible. This reliability is in sharp contrast with our earlier experience with the Hemopump cannula introduced through the groin. Problems of cannula introduction, drive cable fracture, hemolysis, and cannula displacement were too frequent with this groin cannula [10, 12, 13]. The only device-related complication in this series, with the transthoracic 24F cannula, was the thrombosis of a cannula that was left in place too long because of a nonrecovering myocardium. The transthoracic 24F Hemopump is easy to implant and remove. The surgical procedure itself is short and simple, requires no cardiopulmonary bypass, and can be done by any cardiac surgeon. The device is relatively inexpensive compared with other assist devices for mechanical support.

However, the Hemopump did not perform well in all cases. Five patients died within the first 24 hours in low cardiac output. In these patients the Hemopump did unload the ventricle (decrease in left atrial pressure) but the increase in cardiac index was not sufficient to maintain organ perfusion (mean increase in cardiac index was 0.516 compared with 1.377 L • min^-1 • m^-2 for the other patients; p = 0.0275). All patients with a maximum cardiac index less than 2.5 L • min^-1 • m^-2 after 12 hours of Hemopump support died within the first 24 hours. The maximum cardiac index seemed to be the best parameter to express the quality of support, as the parameters increase in cardiac index and increase in mean arterial blood pressure are more dependent on the preassist state. The better the patient's condition was, the smaller the gain will be by starting the mechanical assistance. Also, reduction in left atrial pressure is an unreliable parameter of prognosis as the left atrial pressure was as well reduced in these 5 patients as in the better assisted patients. In 1 of these 5 early failures the diagnosis of right ventricular failure was made. Three of these patients were known to have left ventricular hypertrophy, and we believe that the Hemopump performance was reduced by impaired inflow in these reduced ventricular cavities. In cases of left ventricular hypertrophy, where the cardiac failure is often rather diastolic than systolic, the concept of an intraventricular unloading device is not appropriate. We therefore consider left ventricular hypertrophy as a relative contraindication to the use of the Hemopump. Absolute contraindications are (1) the presence of cloth in the left ventricle, (2) the presence of necrotic tissue in the left ventricle (postinfarction ventricular septal defect), and (3) the presence of an aortic valve prosthesis [12, 14]. In this series we did use the device in 1 patient with an aortic bioprosthesis. This valve, however, was constructed of the patient's own pericardial tissue and it was judged that the leaflets were sufficiently pliable to permit the passage of the cannula and prevent a leak around the cannula.

Transesophageal echocardiography was a helpful tool to assess myocardial function. It was used in the shock phase during the introduction of the Hemopump, which allowed us to confirm the intraventricular position of the Hemopump cannula and to assess the unloading effect of the start of the assisted circulation. As long as the Hemopump was used at maximal speed for complete unloading, transesophageal echocardiography was not performed, in an attempt to reduce infection and trauma risks. During weaning the cardiac function was judged hemodynamically and with transesophageal echocardiography. The Hemopump was reduced to its lowest speed but never turned off, as a completely stopped Hemopump induces serious aortic insufficiency. Weaning was possible in 50% and hospital mortality was 75%, which is comparable with other series of mechanical support for recovery of the failing postcardiotomy heart [11, 15–17]. Clearly, the overwhelming effect of the preassist state and the underlying conditions have to be considered in this area of mechanical support. Defining those patients who will improve by mechanical support remains the greatest challenge. It is our policy to support all patients in cardiac shock despite maximal inotropic support and IABP. In 2 patients this policy proved to be wrong as they were mechanically supported for 7 days in a perfect hemodynamic state and did not recover at all. Of course, at the moment of Hemopump implantation we cannot predict the ability to recover, and so far no test can differentiate between necrosed and stunned myocardium. With increasing experience in mechanical assistance it might be possible to find reliable predictive factors of mortality as has been suggested for the IABP by Baldwin and associates [18].

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Address reprint requests to Dr Meyns, Department of Cardiac Surgery, Gasthuisberg University Hospital, Herestraat 49, 3000 Leuven, Belgium.

	References

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 

1. Edwards FH, Clark RE, Schwartz M. Coronary artery bypass grafting: The Society of Thoracic Surgeons National Database experience. Ann Thorac Surg 1994;57:12–9.[Abstract]
2. Downing TP, Miller DC, Stinson EB, et al. Therapeutic efficacy of intraaortic balloon pump counterpulsation. Analysis with concurrent ``control'' subjects. Circulation 1981;64(Suppl 2):108–13.
3. Creswell LL, Rosenbloom M, Cox JL, et al. Intraaortic balloon counterpulsation: patterns of usage and outcome in cardiac surgery patients. Ann Thorac Surg 1992;54:11–20.[Abstract]
4. Mehrige ME, Smalling RW., Cassidy DB., et al. Effect of the Hemopump left ventricular assist device on regional myocardial perfusion and function. Circulation 1989;80(Suppl 3):158–66.[Abstract/Free Full Text]
5. Smalling RW, Cassidy DB, Barrett R, Lachterman B, Felli P, Amirian J. Improved regional myocardial blood flow, left ventricular unloading, and infarct salvage using an axial-flow, transvalvular left ventricular assist device. Circulation 1992;85:1152–9.[Abstract/Free Full Text]
6. Shiiya N, Zelinsky R, Deleuze PH, Loisance DY. Changes in hemodynamics and coronary blood flow during left ventricular assistance with the Hemopump. Ann Thorac Surg 1992;53:1074–9.[Abstract]
7. Laschinger JC, Grossi EA, Cunningham JN, et al. Adjunctive left ventricular unloading during myocardial reperfusion plays a major role in minimizing myocardial infarct size. J Thorac Cardiovasc Surg 1985;90:80–5.[Abstract]
8. Wouters PF, Sukehiro S, Möllhoff T, et al. Left ventricular assistance using a catheter-mounted coaxial flow pump (Hemopump) in a canine model of regional myocardial ischaemia. Eur Heart J 1993;14:567–75.[Abstract/Free Full Text]
9. Sukehiro S, Flameng W. Effects of left ventricular assist for cardiogenic shock on cardiac function and organ blood flow distribution. Ann Thorac Surg 1990;50:374–83.[Abstract]
10. Wiebalck AC, Wouters PF, Waldenberger FR, et al. Left ventricular assist with an axial flow pump (Hemopump): clinical application. Ann Thorac Surg 1993;55:1141–6.[Abstract]
11. Wampler RK, Frazier OH, Lansing AM, et al. Treatment of cardiogenic shock with the Hemopump left ventricular assist device. Ann Thorac Surg 1991;52:506–13.[Abstract]
12. Meyns B, Vanermen H, Vanhaecke J, Sergeant P, Daenen W, Flameng W. Hemopump fails as bridge to transplantation in postinfarction ventricular septal defect. J Heart Lung Transplant 1994;13:1133–7.[Medline]
13. Waldenberger FR, Wouters P, Wiebalck A, Flameng W. Use of left-ventricular assist with the Hemopump in cardiac surgery. Cardiology 1994;84:211–5.[Medline]
14. Flameng W, ed. Temporary cardiac assist with an axial pump system. New York: Springer-Verlag, 1991:73–7.
15. Guyton RA, Schonberger JP, Everts PA, et al. Postcardiotomy shock: clinical evaluation of the BVS 5000 biventricular support system. Ann Thorac Surg 1993;56:346–56.[Abstract]
16. Killen DA, Piehler JM, Borkon AM, Reed WA. Bio-Medicus ventricular assist device for salvage of cardiac surgical patients. Ann Thorac Surg 1991;52:230–5.[Abstract]
17. Golding LA, Crouch RD, Stewart RW, et al. Postcardiotomy centrifugal mechanical ventricular support. Ann Thorac Surg 1992;54:1059–64.[Abstract]
18. Baldwin RT, Slogoff S, Noon GP, et al. A model to predict survival at time of postcardiotomy intraaotic balloon insertion. Ann Thorac Surg 1993;55:908–13.[Abstract]

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Bart P. Meyns Paul T. Sergeant Willem J. Flameng Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meyns, B. P. Articles by Flameng, W. J. Search for Related Content PubMed PubMed Citation Articles by Meyns, B. P. Articles by Flameng, W. J.