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Eur J Cardiothorac Surg 2005;28:717-723
© 2005 Elsevier Science NL
a Department of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany
b Department of Cardiology, University of Heidelberg, Heidelberg, Germany
c Institute of Pathology, University of Heidelberg, Heidelberg, Germany
Received 18 May 2005; received in revised form 16 July 2005; accepted 27 July 2005.
* Corresponding author. Tel.: +49 6221 5636191; fax: +49 6221 565585. (Email: achim_koch{at}med.uni-heidelberg.de).
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Abstract |
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 Top Abstract 1. Introduction2. Materials and methods3. Results4. Discussion5. ConclusionReferences |
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Key Words: Bicaval heart transplantation • Tricuspid regurgitation
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1. Introduction |
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. ConclusionReferences |
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However, anastomosis according to the Lower-Shumway technique of cardiac transplantation create enlarged atrial cavities with abnormal geometry between donor and recipient atrium. It has been claimed, that loss of normal atrial geometry is responsible for the occurrence of post-transplant mitral- and tricuspid regurgitation and poor preservation of sinus node function [19].
In order to retain normal shaped atria with preserved atrial contractility, sinus node function and competent atrio-ventricular valves different techniques of cavoatrial and pulmonary venous-atrial anastomoses were introduced into clinical practice in the early 1990's [12].
This study was designed to compare the long-term difference in atrio-ventricular valve competence between the standard and total orthotopic heart transplantation technique.
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2. Materials and methods |
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. ConclusionReferences |
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Additional immuno-suppression was continued with a triple therapy including methyl prednisolone, azathioprine and cyclosporine A. Cyclosporine A was started orally at a dose of 2 mg/kg and was adjusted to keep the whole blood trough levels between 200 and 300 ng/ml in the initial postoperative period. During the first postoperative year serum trough levels were maintained at 150 ng/dl for monoclonal assays. Additionally oral azathioprine was given at a dose of 0.5–1 mg/kg on condition that leucocyte count was over 4000/µl. Patients received 500 mg methyl-prednisolone before aortic cross clamp was released. A starting dose of 100 mg methyl-prednisolone per day was tapered 5 mg every second day up to a maintenance dose of 10 mg/d for the first postoperative year.
Rejection monitoring was performed by standard Stanford routine endomyocardial biopsy scheme (EMB) and graded according to the ISHLT grading system (M.E. Billingham). Endomyocardial biopsies were performed weekly for the first 4 weeks. Afterwards, the intervals between the biopsies were prolonged stepwise to yearly biopsies, taking into account previous rejection episodes. Additional biopsies always were performed when rejection was clinically suspected. Endomyocardial biopsies were performed through a percutanous V. brachiocephalica approach using a Caves biotome in a strictly aseptic technique. Biopsy specimens were obtained under fluoroscopic guidance from the septum and the apex of the right ventricle.
In a rejection higher than grade 2, initial treatment with oral methyl-prednisolone was given. Patients in both groups received 1000 mg methyl-prednisolone daily for three days followed by a control biopsy.
2.3 Echocardiography
The recipients had routine echocardiographic follow-up examinations during the first month, the first, third, fifth, seventh, tenth and more than 10 years after transplantation.
Echocardiographic measurements were performed using a Hewlett-Packard Sonos 5500 ultrasound (Hamburg, Germany) imaging system with a 2–5 MHz transducer from a standard window in the left lateral position. Valve competence was assessed by colour Doppler four-chamber view (see Table 2 ). Right and left ventricular ejection fraction was estimated visually and graded in impaired and not impaired. Left ventricular end-diastolic and end-systolic volumes were calculated. The dimensions of the ventricles and atria were measured in the M-mode.
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2.5 Statistics
Statistical analysis was performed by using SPSS software (Version 11,0; SPSS Inc, Chicago IL). Results are given as mean values ± SD unless indicated otherwise.
A P-value of <0.05 represents statistical significance.
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3. Results |
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. ConclusionReferences |
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Both group showed comparable data for age at transplantation, weight, height, pre-transplant diagnosis, donor-recipient height, weight ratio and donor age.
There was no statistical significant difference between the two groups in operative mortality and long-term survival.
The total operation time of 285 ± 109 min in the total orthotopic group was significantly longer than in the standard group 232 ± 63 min (P< 0,05). There was also a significantly increased cardiopulmonary bypass time and aortic cross-clamp time in the total orthotopic group (144 ± 55 min) (P<0,05). The total orthotopic technique prolonged the cold ischemic time also significantly (P<0.05).
The significantly longer operation times and the higher blood loss of the TOHT-group can be seen as a result of the significantly higher rate of redo-operations (42%, P<0.01).
3.1 Hemodynamics
Hemodynamic data are summarized in Table 3
and in Fig. 1
A–E. There were no significant differences between the groups regarding mean pulmonary arterial pressure, pulmonary capillary wedge pressure and pulmonary vascular resistance. In both groups pulmonary vascular resistance decreased from the postoperative examination to the examination after 7 years, but this difference did not reach significance. The postoperative cardiac output was increased significantly for the TOHT-group relative to the standard group in postoperative year 3 and 7. This is probably not accounted by differences in preload as central venous pressure were similar. During the other periods the difference did not reach significance.
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The tricuspid insufficiency was in three patients severe enough to cause prosthetic valve replacement.
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4. Discussion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. ConclusionReferences |
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4.2 Significance of tricuspid regurgitation
Recent studies report about a high incidence of moderate to mild degrees of tricuspid regurgitation (TR) after orthotopic heart transplantation. A high prevalence of TR in healthy subjects can be also found as a result of great sensitivity of echocardiographic colour-flow mapping. Trivial or mild degrees of TR after HTx are thought to have a benign course. The overall prevalence ranges from 47 to 98% in echocardiographic series. But severe TR occurs rarely and is refractory to medical management [1,8,10,24]. DeSimone reports that TR can occur immediately after transplantation and can be caused in turn by a reduction in systolic annulus shortening. They found the degree of mitral regurgitation was usually mild, whereas TR ranged from mild to moderate [11]. The Wythenshawe group reported that recipients who underwent operation by the standard technique had always a significantly higher severity of TR than bicaval technique did. In the long-term follow up after HTx severe TR contributes to RV-volume loading and patients are at high risk for the development of right heart failure, which is associated with significant morbidity. Particularly in recipients with persistent pulmonary hypertension after surgery presence of TR might have a detrimental effect on right ventricular cardiac performance with lower cardiac index and higher atrial filling pressures [1,8,16,22].
4.3 Explanation of TR
Most widely accepted explanation for TR is tricuspid leaflet or chordal damage during endomyocardial biopsy. In almost all patients undergoing tricuspid valve replacement reported ruptured or torn chordae were identified at the time of operation, further supporting the theory that severe TR is biopsy induced. The chordae tendineae usually arise from the papillary muscles but also from the septal wall and thus are subject to trauma by the biotome each time it traverses the tricuspid valve [8,24]. The influence of number and degree of rejection episodes on the incidence of TR is discussed controversely [2,8]. Especially in the late postoperative period the recipients in our institution developed moderate and severe tricuspid insuffiency if they were transplanted in the standard technique. This group had a higher degree in rejection episodes and a larger number of endomyocardial biopsies. However, our results cannot definitely answer the question if more rejection led to more biopsies that increased the risk of traumatic tricuspid insufficiency. Both groups did not differ in immunosuppression but it may be speculative if a better cardiac output in the total orthotopic group and as a result a better renal function allows a more intensive immunosuppression.
Aziz identified in a multivariate analysis standard technique as the most independent predictor for early and late TR. Apart from a distortion of the tricuspid annulus due to disturbed geometry of the right atrial anastomosis, there might be an influence of ischemic injury to the papillary muscles at the time of transplantation [1,24,25].
Severe degrees of TR may cause intractable right heart failure which itself may contribute to early and late morbidity after heart transplantation.
4.4 Pulmonary hypertension
The transplanted heart is directly after weaning from cardiopulmonary bypass exposed to elevated pulmonary pressures of the recipient. This afterload mismatch may enhance the risk of right ventricular failure. The occurrence of TR can be explained by persistent chronic pressure overload due to persistent pulmonary hypertension and a volume overload due to primary or secondary tricuspid insufficiency [1].
In contrast to our data other groups report about elevated right-sided pressures in the recipients with moderate to severe TR in right heart catheterisation. They also found standard technique recipients to have higher right-sided pressures compared to the bicaval technique recipients [3]. In both of our groups mean pulmonary arterial pressures were on an equal level and pulmonary vascular resistance was decreasing with time.
4.5 Right atrial function
To obtain the functional integrity enhances the function of the right atrium (RA). The loss of right ventricular filling pattern through asynchronous contraction of donor and recipient atria after use of standard technique contributes to diminished stroke volume. Bicaval technique offers a more physiologic RA size and minimises geometric mismatch between donor and recipient atria [20,23].
Diminished forward systolic vena cava flow has been proposed as a sign of acute cardiac rejection. Increased late diastolic tricuspid flow in the patient with bicaval technique indicated more rigorous RA contraction following by better atrial relaxation. RA contraction may be less vigorous in recipients of the standard technique as a result of atrial sutures and greater size [3,24].
4.6 Right heart function
The improved right heart hemodynamic of the TOHT-recipients reflects the improved right-ventricular function of these patients. This can be caused by a better atrial geometry with a lower incidence of tricuspid-insufficiency. In contrast right atrial size was significantly enlarged in patients with standard atrial anastomoses, this probably contributes to the development of TR by increasing wall tension and tricuspid annular size during late systole. Patients with atrial anastomoses and tricuspid regurgitation could have been shown to have significant increases of right atrial pressure during exercise. Only patients without TR were able to achieve 100 watts of workload providing some evidence that TR may influence exercise capacity [21].
Severe TR has been previously shown to have a deleterious effect on right ventricular function. Right ventricular volume loading combined with right ventricular dilatation can cause right ventricular dysfunction. This may lead to a septal displacement and contributes diminished left ventricular filling. So, ventricular interdependence may lead to LV-diastolic dysfunction. Furthermore, in dilative cardiomyopathy left ventricular function after standard technique HTx is altered by left atrial dysfunction and lack of atrial filling waves of the atrial cuff. So, a small left atrial cuff of the recipient with the bicaval technique and dilative Cardiomyopathy lowers the incidence mitral valve dysfunction [2].
4.7 Surgical technique
The standard surgical technique for heart transplantation first described by Lower, Stofer and Shumway has been used worldwide for most heart transplantations since 1967 [17]. This technique is very attractive in its simplicity and offers a highly reproducible surgical procedure. However, some immanent disadvantages of this technique have been previously described:
The standard therapy requires more pacemakers has a higher incidence of pulmonary hypertension, increased peak oxygen consumption and a greater extent of mitral- and tricuspid regurgitation [5].
But it also creates enlarged atriae with a sort of snowman aspect of the left atrium. The suture lines may protrude into the atrial cavity. Combined with asynchronous contraction between enlarged donor and recipient atrium blood stasis and consecutive spontaneous echo-contrast can be promoted. Presence of spontaneous echo contrast has been shown to increase thrombembolic risk in orthotopic heart transplantation [6]. Sievers reports about the absence of spontaneous echo in bicaval patients. Standard technique: high incidence of spontaneous echo contrast SEC, left atrial enlargement is thought to be responsible for blood stasis.
Embolic events only occurred in the standard group. None of the patients transplanted with the total heart technique showed signs of peripheral embolism. Pulmonary capillary wedge pressure was not significantly different between both groups and was not increased with the enlargement of the left atrium in the standard group.
In 1991 Dreyfus introduced the total orthotopic technique into clinical practice [6]. In contrast to the Lower–Shumway technique it offers a total anatomical transplantation of the whole heart and preserves normal morphology of both atria. A potential problem might be an increased aortic-cross-clamp time for completion of two additional anastomoses. In our experience the cross-clamp time was increased significantly. Implantation time was significantly longer, however, in centers employing the total technique [1]. Different authors agree that bicaval anastomoses decrease atrial size and have less tricuspid regurgitation. Especially total orthotopic transplantation provides better left ventricular function, a significantly better cardiac index, more frequently non-paced normal SR, demonstrates clinical benefit, less hospitalisation time and a strikingly better survival [2,4,7,13,18,21]. Studies underline early and long-term influence of the surgical technique.
The pulmonary venous anastomoses have to be performed very carefully to prevent bleeding from their inaccessible medial aspect. Blood loss was not increased by the use of total orthotopic heart transplantation technique [6]. Blood-loss was significantly lower in the bicaval group both, at 24 h and overall [13].
When sewing the two caval anastomoses the use of an interrupted suture line helps effectively to prevent the otherwise inevitably purse-stringing [15]. Generally, the incidence of caval stenosis seems to be quite rare and not to be a reason to avoid bicaval procedure [18].
4.8 Rhythm disturbances
The incidence of need for permanent postoperative pacing range from 0 to 10%. The lowest incidence of pacemaker use was reported among centres employing the total technique. After weaning from extra-corporal circulation modified operation technique for orthotopic transplantation leads immediately to a stable sinus rhythm [2,13,15]. Brady-cardia in the early postoperative period is a well described phenomenon. Little is known about brady-cardia occurring in the late postoperative period. Grant describes the incidence of symptomatic brady-cardia with 5% one year after transplantation. Experience with permanent pacing tends to be small in any given institution [9,14]. Potential risk factors for permanent pacing may be disruption of sino-atrial nodal blood supply, long donor ischemic time, long aortic cross clamp time, longer postoperative temporary pacing time and high grades of rejection in the first month. Temporary atrial pacing was more frequently required in those patients who had been receiving pre-transplantation amiodarone. Reduced graft function may also occur due to denervation of the graft and rhythm disturbances [8,14].
In summary, TOHT helps to decrease atrial size, preserves better right and left heart function, decreases tricuspid regurgitation. TOHT is sometimes thought to cause bleeding problems and pulmonary vein stenosis. We did not observe these problems in our transplant programme. To avoid potential bleeding problems of the pulmonary veins anastomoses, they are coagulated circularily and the suture lines are performed very carefully.
None of our recipients developed a pulmonary vein stenosis postoperatively. If the atrial orifice and the pulmonary vein flap are large enough, a purse-string effect of the sutures can be safely prevented. Under these regards we strongly encourage other groups to perform the only ‘physiological’ implantation technique, the total orthotopic heart transplantation.
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5. Conclusion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. ConclusionReferences |
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Footnotes |
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Presented at the joint 18th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 12th Annual Meeting of the European Society of Thoracic Surgeons, Leipzig, Germany, September 12–15, 2004. 
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. ConclusionReferences |
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