T Aziz

Bicaval and standard techniques in orthotopic heart transplantation: Medium-term experience in cardiac performance and survival

OBJECTIVE The aim of this study was to compare the medium-term results of right heart pressures, tricuspid valve dysfunction, overall cardiac performance, and survival between the bicaval and standard techniques. METHOD Between 1991 and 1997, 201 heart transplantations were performed in our center. Right heart catheterization was performed up to 12 months after transplantation. Echocardiography was used to assess left ventricular and tricuspid valve function. RESULT The standard technique was used in 105 cases, and the bicaval technique was used in 96 cases. There was no difference in the age, preoperative parameters, pulmonary hemodynamics, or ischemic time between the 2 groups. Right atrial pressure (4.3 +/- 4.0 mm Hg for the bicaval vs 10.9 +/- 4.8 mm Hg for standard technique) and mean pulmonary artery pressure (17.5 +/- 5.3 mm Hg and 22.5 +/- 5.2 mm Hg, respectively) were lower for the bicaval recipients up to 12 months after the operation (P =.001 and. 01, respectively). Left ventricular ejection fraction was higher for the recipients of the bicaval technique up to the most recent measurement (P =.005). The prevalence of moderate or severe tricuspid regurgitation was higher in the recipients of the standard technique up to the most recent measurement (28% vs 7%; P =.02). The actuarial survival at 1, 3, and 5 years was 74%, 70%, and 62% for the recipients of the standard technique versus 87%, 82%, and 81% for the recipients of the bicaval technique (P <.03, <.04, and <.02, respectively). CONCLUSION The bicaval technique maintains good left ventricular function, lower incidence and severity of tricuspid valve dysfunction, and improved survival compared with the standard technique.

Risk factors for tricuspid valve regurgitation after orthotopic heart transplantation

BACKGROUND Tricuspid regurgitation (TR) may occur following orthotopic heart transplantation (OHT) and although a number of etiological factors have been suggested, the relative contribution of each of these remains to be elucidated. We aimed to assess the risk factors for TR in our 10-year experience of orthotopic heart transplantation (OHT). METHODS OHT was performed in 249 patients (161 by the standard technique and 88 by the bicaval technique). TR was assessed using transthoracic color Doppler echocardiography. RESULTS Recipients who underwent operation by the standard technique displayed higher incidence of moderate and severe TR than did bicaval-technique recipients. The development of early TR was also correlated to rejection greater than or equal to grade 2, preoperative raised transpulmonary gradient, and raised pulmonary vascular resistance. Risk factors for late TR were standard technique (p < 0.0001), number of rejection greater than or equal to grade 2 (p < 0.004), and the total number of heart biopsies (p < 0.02). Recipients with moderate and severe TR revealed elevated right-side pressures and advanced New York Heart Association statues compared to those with no, trivial, or mild TR. CONCLUSIONS Various factors contribute to TR after OHT, the prevalence of which might be lowered by adopting the bicaval technique, early treatment of rejection, and reduction of the number of biopsies performed.

Transforming growth factor β in relation to cardiac allograft vasculopathy after heart transplantation

Background: Cardiac allograft vasculopathy is a frequent sequel to cardiac transplantation, but the role of cytokines on the subsequent development of vasculopathy is still largely unknown. Methods: We retrospectively studied 172 heart transplant recipients to investigate the relationship between the development of vasculopathy and various factors including the presence of transforming growth factor (TGF-β) in the graft. Endomyocardial biopsy specimens were stained with antibodies for TGF-β and CD+68, and a TGF-β staining score was derived. Vasculopathy was diagnosed by angiography and rejection was graded according to the International Society of Heart and Lung Transplantation classification. TGF-β1 genotype was determined by polymerase chain reaction analysis of DNA. Results: After a mean follow-up period of 68 ± 32 months, the prevalence of significant vasculopathy was 52%. The TGF-β staining score was higher in patients with more severe vasculopathy (95% confidence interval = 8.9-12.1) than in those who showed minimal or mild vasculopathy score changes of more than 7 (95% confidence interval = 3.4-5.1), P = .0001. TGF-β expression correlated with the degree of vasculopathy (r = 0.73, P < .0007) during the study period. Risks for vasculopathy were recipient homozygous TGF-β genotype, recurrent rejection, recipient history of ischemic heart disease, donor male sex, old donor age (years), and donor history of subarachnoid hemorrhage. Conclusion: A strong association exists between the expression of TGF-β in cardiac biopsy specimens and the development of vasculopathy. TGF-β in the cardiac allograft is related to its genotype and to the number of rejection episodes. Strategies to down-regulate TGF-β production might improve the outcome of cardiac allografts. (J Thorac Cardiovasc Surg 2000;119:700-8)

Orthotopic cardiac transplantation technique: a survey of current practice

BACKGROUND The Lower and Shumway technique has been the gold standard for orthotopic heart transplantation (OHT) for the past 35 years. In the last decade the bicaval and total techniques have been introduced but it is unclear how these alternative techniques have influenced the current surgical practice of OHT. METHODS A worldwide survey of 210 International Society of Heart and Lung Transplantation centers was conducted by questionnaire: 169 replies were received; a response rate of 80%. RESULTS Seventy-four centers (44%) use a combination of more than one technique with the remaining centers (n = 95 centers) employing one technique exclusively. The bicaval technique is the most frequently used technique in the majority of transplant procedures in 92 (54%) centers. In only 38 centers (22%), the standard technique was the most frequently employed technique. The total technique was the choice in 8 centers (5%). The maximum acceptable ischemic time varied from 3 to 9 hours with a median of 5.7 hours. Only 92 centers (54%) do not use cardioplegia during implantation. CONCLUSIONS Since its introduction, the bicaval technique has become the most commonly used procedure for OHT. The long-term advantage of right atrial preservation with the bicaval technique will require further studies.

Clinical significance of Tricuspid valve dysfunction after orthotopic Heart transplantation

OBJECTIVES Tricuspid regurgitation (TR) is common after heart transplantation (OHT), but its clinical relevance is undetermined. This study documents the clinical progress of patients with TR after OHT in relation to the severity of TR. METHODS We studied 238 transplant recipients who had survived for at least 12 months after OHT. Tricuspid regurgitation was graded clinically and by assessing regurgitant jet area. Recipients were divided into those with no TR Group 1 (n = 64), those with sub-clinical TR (TR absent clinically and regurgitant jet area <25%, Group 2 (n = 89), and those with clinical TR (with clinical TR or regurgitant jet area > or =25%, Group 3 (n = 85). RESULTS We found no significant difference among the groups in terms of age, or pre-operative events. At 12 months after OHT, mean right atrial and pulmonary artery pressures were higher in Group 3 than in Group 1 or Group 2 (p = 0.005 and 0.03, respectively). Right ventricular end-diastolic and end-systolic volumes were smaller for recipients in Groups 1 and 2 compared with those in Group 3 (p = 0.01 and 0.02). The annual development of renal impairment was 0.019 (95% confidence interval [CI], 0.014-0.029), 0.026 (95% CI, 0.022-0.62), and 0.613 (95% CI, 0.346-0.756) in Groups 1, 2, and 3, respectively (p = 0.02). At the most recent follow-up, mean New York Heart Association class for Group 1 was 1.4, for Group 2 was 1.7, and for Group 3 was 2.7 (p = 0.04). CONCLUSIONS The integrity of the tricuspid valve has a significant impact on long-term clinical progress of OHT recipients. Recipients with significant TR are more symptomatic and have poorer right-sided heart function compared with those with mild or no TR.

Cardiac transplantation for cardiomyopathy and ischemic heart disease: differences in outcome up to 10 years

BACKGROUND Ischemic heart disease (IHD) and cardiomyopathy (CM) are the most common indications for heart transplantation. The aim of this study was to investigate the difference in clinical outcome between these two groups. METHODS At our institution between 1987 and 1998 transplantation was performed in 133 patients with IHD and 87 with CM. Follow-up was complete for all patients (mean 87 months). RESULTS Mean age at time of surgery was 51 +/- 5 years for IHD versus 39 +/- 9 years for CM recipients (p = 0.02). There was no difference in donor age, donor gender, or pre-operative hemodynamics between the two groups. The operative mortality was 11.2% in IHD recipients and 10.6% in CM recipients (p = 0.9). No differences were observed in intra-cardiac pressures or incidence of renal dysfunction, infection, or malignancy between the two groups. The incidence of peripheral vascular incidents was significantly higher for IHD recipients (13% vs 3%, p = 0.02). At 10 years, the incidence of coronary artery disease was 35% and 9%, respectively (p = 0.02). Mean NYHA status was 2.0 +/- 0.3 and 1.1 +/- 0.2 for IHD and CM recipients, respectively (p = 0.013). The actuarial survival at 1, 5, and 10 years was 77%, 62%, and 39% for IHD recipients compared with 85%, 82%, and 80% for CM recipients (p = 0.7, p < 0.0001 and p < 0.0001, respectively). CONCLUSION After heart transplantation, medium- and long-term outcome is significantly better for CM than IHD recipients. In view of limited donor availability, it is appropriate to explore more vigorously alternative treatments for patients with severe ischemic left ventricular dysfunction.

Heart transplantation for peripartum cardiomyopathy: a report of three cases and a literature review.

Peripartum cardiomyopathy is a devastating medical condition and carries a mortality of up to 60% with medical treatment. The authors describe their experience of successful outcome of three cases with heart transplantation and review the literature. The importance of performance of endomyocardial biopsy for all peripartum cardiomyopathy patients is emphasized. It is recommended that heart transplantation should only be offered to myocarditis negative patients.

Transforming growth factor β and diastolic left ventricular dysfunction after heart transplantation: Echocardiographic and histologic evidence

BACKGROUND The mechanism for chronic left ventricular diastolic dysfunction in the non-rejecting cardiac allograft has not been fully studied. OBJECTIVES The purposes of this study were to analyze the significance and frequency of left ventricular diastolic dysfunction after heart transplantation and to examine the involvement of fibrotic cytokines (transforming growth factor beta [TGF-beta]) in development of clinical and echocardiographic changes in cardiac allograft recipients. METHODS We studied 152 heart transplant recipients who had survived for at least 24 months. We compared histopathologic findings (staining of endomyocardial biopsy specimens using hematoxylin and eosin, and polyclonal antibodies expressed as TGF-beta score), left ventricular function (Doppler echocardiography), and clinical course (New York Heart Association [NYHA] status). We classified patients into Group 1 (n = 41 recipients) with a restrictive filling pattern, mitral deceleration time (MDT) <140 milliseconds, and Group 2 (n = 111 recipients), MDT >or=140 milliseconds. RESULTS The MDT was 122 +/- 7 milliseconds in Group 1 compared with an MDT of 177 +/- 17 milliseconds in Group 2 (p = 0.0003). Group 1 showed significant immunohistochemical staining in endomyocardial biopsy specimens (a mean TGF-beta score of 9.1 +/- 1.2 for Group 1 compared with a mean TGF-beta score of 3.6 +/- 0.8 for Group 2 p = 0.001). The TGF-beta expression correlated inversely with both MDT and isovolumic relaxation time (r = -0.77, p = 0.0004, and r = -0.69, p = 0.004, respectively). Mean NYHA status in Group 1 recipients was 2.2 +/- 1.1 compared with 1.37 +/- 0.6 for Group 2 (p = 0.006). CONCLUSIONS Transforming growth factor beta expression in cardiac allografts is associated with impaired left ventricular diastolic function. The pathogenesis of diastolic dysfunction may be an aberrant repair process after rejection-caused TGF-beta expression in the allograft.

Pulmonary vein gas analysis for assessing donor lung function.

BACKGROUND Radial artery oxygenation (PaO2) is the standard method for assessing potential lung donors. This study was proposed to assess the use of pulmonary vein gases (PvO2) in selection of donor lung for transplantation. METHODS We studied 170 lungs from 85 consecutive donors. Lungs were classified into group A, PaO2 and PvO2 > 300 mm Hg; group B, PaO2 < 300 mm Hg, and PvO2 > 300 mm Hg; and group C, PvO2 < 300 mm Hg. RESULTS Lungs retrieved from group A and group B were used for transplantation. Allograft function, assessed by the arterial and alveolar oxygen tension ratio, was similar at 12 hours and at 24 hours after operation (0.69, 0.73, vs 0.70, 0.71, for groups A and B, respectively (p = 0.8, 0.7, respectively). Similar radiologic appearance was seen in both groups (p = 0.2). Median duration of intubation was also similar (p = 0.6). The 30-day mortality rate was 12% versus 11.3% (p = 0.8), and 1-year survival rate was 80% versus 82% (p = 0.8) for recipient received lungs from group A and B donors, respectively. CONCLUSIONS Selective pulmonary veins analysis gives an accurate assessment of individual gas exchange in comparison with arterial PaO2, identifying more potential donor lungs for transplantation.

Transforming growth factor beta and myocardial dysfunction following heart transplantation

OBJECTIVE We analyzed the role of transforming growth factor-beta (TGF-beta), a fibrogenic cytokine, in the development of left ventricular diastolic dysfunction following heart transplantation. METHODS We studied 152 heart transplant recipients who had survived for at least 24 months. We compared histopathological findings (staining of endomyocardial biopsy specimens using Hematoxylin Eosin and polyclonal antibodies), left ventricular function (Doppler echocardiography) and clinical course (NYHA status). Patients are classified into group A (n=56 recipients) with immunohistochemical TGF-beta staining score >7 and group B (n=96 recipients) with a staining score <7. RESULTS Doppler echocardiographic evaluation demonstrated greater impairment of left ventricular diastolic function in recipients with higher TGF-beta staining score. The average mitral deceleration time was 129+/-6 ms for recipients group A compared to 167+/-15 ms in group B. While the mean isovolumic relaxation time was 65+/-8 ms for patients in group A compared with 82+/-6 ms for recipients in group B (P=0.0004 and 0.005, respectively). Immunohistochemical scoring correlated inversely with both mitral deceleration and isovolumic relaxation times (r=-0.74, P=0.0004 and r=-0.66, P=0.004, respectively). Mean NYHA status was 2.7+/-1.3 for group A compared to 1.17+/-0.4 in group B was (P=0.002). Five years follow-up revealed persistent left ventricular diastolic impairment for recipients with higher immunohistochemical staining score. Mitral deceleration time and isovolumic relaxation time were 118+/-11 and 62+/-7 ms for group A compared to 156+/-12 and 80+/-5 ms for group B, P=0.006 and P=0.01, respectively. The actuarial development of subsequent coronary artery disease (> 50% stenosis) was 17 and 29% for recipients in group A compared to 4 and 6% for recipients in group B at 3 and 5 years follow-up, respectively (P=0.01 and P=0.005, respectively). CONCLUSIONS TGF-beta expression in cardiac allografts is associated with impaired graft function and limited survival. The pathogenesis of diastolic dysfunction may be an aberrant repair process following rejection due to increased TGF-beta expression in transplant recipients.