Experience with beta-blocker therapy in patients with advanced heart failure evaluated for HTx.

BACKGROUND: The aim of this study was to review our experience with beta-blocker therapy on top of high-dose angiotensin-converting enzyme inhibitors (ACE-I) in patients with advanced heart failure evaluated for heart transplantation, and to question the value of intended heart transplantation for patients receiving this therapy. METHODS: Three hundred eighteen patients (New York Heart Association (NYHA) function class III 34%, class IV 66%, average left ventricular ejection fraction (LVEF) 16%, and average cardiac index 2.2 l/min per m(2) at time of referral) were treated with digitalis, loop diuretics, maximally uptitrated ACE-I, beta-blockers (if tolerated), and intravenous support (if needed). After 3 months, patients were retrospectively stratified into those receiving beta-blockers plus ACE-I (Group A, n = 126), ACE-I (Group B, n = 135), and ACE-I plus intravenous support (Group C, n = 57). Endpoint 1 of the study was combined urgent heart transplantation, mechanical assist device implantation, and pretransplant death during a follow-up of 12 to 48 (mean 19 +/- 11) months. Endpoint 2 was posttransplant mortality up to 48 (mean 14 +/- 8) months. RESULTS: In the pretransplantation period the survival rate was 58% and the mortality rate was 20%. Between Groups A and B there was a significant difference in mortality (9% vs 27%, p = 0.001) due to a lower sudden-death rate in Group A (6% vs 17%, p < 0.01). While between Groups A and C all event rates of Endpoint 1 differed significantly, between Group C and Group B total mortality (30% vs 27%) was similar. However, in Group C urgent heart transplantation (HTx) was more often performed than in Group B (54% vs 11%, p < 0.0001). Seventy of 318 patients (22%) underwent heart transplantation (16% urgent, 6% elective). Posttransplant actuarial survival of the entire transplanted cohort (n = 70, 12 deaths) was significantly lower (log rank p < 0.01) than event-free survival in Group A (n = 126, 18 events), significantly higher (log rank p < 0. 0001) than event-free survival in Group C (n = 57, 34 events), and similar to that in Group B (n = 135, 52 events). CONCLUSION: This experience suggests that it may be particularly useful to add a beta-blocker to ACE-I therapy in patients referred for heart transplantation. In patients who tolerate this treatment, heart transplantation does not seem to provide additional survival benefit in the short term (2 years).     

Late pacemaker requirement after pediatric orthotopic heart transplantation may predict the presence of transplant coronary artery disease.

BACKGROUND: Few data are available regarding pacemaker implantation after pediatric orthotopic heart transplantation. The purpose of this study was to assess the incidence, indications and associations with regard to pacemaker placement in children who have undergone orthotopic heart transplantation. METHODS: We performed a retrospective study of all patients undergoing orthotopic heart transplantation at our institution from October 1984 to March 2001. Data obtained included demographics, indications for pacemaker, presence of transplant coronary artery disease and long-term follow-up. Patients were divided into: Group 1, patients requiring a pacemaker within 3 months of transplantation; and Group 2, patients requiring a pacemaker beyond 3 months. RESULTS: Pacemakers were required in 7 of 106 (6.6%) transplant recipients. Pacing indications for patients in Group 1 (n = 2) were persistent bradycardia with pause-related ventricular arrhythmia and atrial flutter with resultant sinus pauses of up to 4 seconds. In Group 2 patients (n = 5), indications for pacing were high-grade atrioventricular (AV) block in 1 patient and episodic sinus pauses up to 3.3 seconds associated with syncope/dizziness in the remaining 4 patients. All patients in Group 2 had transplant coronary disease diagnosed within 1 year of pacemaker implantation. All had resolution of symptoms and no complications after implantation. CONCLUSIONS: Pacemakers are infrequently required after cardiac transplantation in children. Despite not meeting classic symptomatic sinus bradycardia criteria, pacemaker placement should be considered post-transplantation in patients with episodic sinus pauses and dizziness or syncope. Patients who present with the aforementioned symptoms or high-grade AV block should be evaluated closely for the presence or development of transplant coronary artery disease, as it may be their first symptom.     

Bridge to transplantation with the Jarvik-7 (CardioWest) total artificial heart: a single-center 15-year experience

BACKGROUND: At our institution, the total artificial heart (TAH) Jarvik-7 (CardioWest) has been used since 1986 as a bridge to transplantation for the most severely ill patients with terminal congestive heart failure. METHODS: Between 1986 and 2001, 127 patients (108 males, mean age 38 +/- 13) were bridged to transplantation with the Jarvik-7 TAH. All were in terminal biventricular failure despite high-dose inotropic support. Nine patients had a body surface area (BSA) of <1.6 m(2). In Group I patients (78%), the etiology of cardiac failure was dilated cardiomyopathy, either idiopathic (n = 60) or ischemic (n = 38). The other 29 patients (Group II) had disease of miscellaneous origin. We analyzed our experience with regard to 3 time periods: 1986 to 1992 (n = 63); 1993 to 1997 (n = 36); and 1998 to 2001 (n = 33). RESULTS: Although Group II patients represented 30% of indications before 1992, they comprised only 15% during the 2 subsequent periods. Duration of support for transplant patients increased dramatically after 1997, reaching 2 months for the most recent period (5 to 271 days). In Group I, the percentage of transplanted patients increased from 43% before 1993 to 55% between 1993 and 1997, and reached 74% thereafter. The major cause of death was multiorgan failure (67%). The clinical thromboembolic event rate was particularly low with no instance of cerebrovascular accident and 2 transient ischemic attacks. Total bleeding complication rate was 26%, including 2 deaths related to intractable hemorrhage and 2 others related to atrial tamponade. The cumulative experience was 3,606 total implant days with only 1 instance of mechanical dysfunction. CONCLUSIONS: TAH is a safe and efficient bridge for patients with terminal congestive heart failure awaiting cardiac transplantation.     

Outcome of children with end-stage congenital heart disease waiting for cardiac transplantation.

BACKGROUND: End-stage congenital heart disease (CHD) is a major indication for pediatric cardiac transplantation. The objective of the study was to evaluate pre-transplant outcome of children with CHD. METHODS: The clinical profile and outcome of patients with CHD <20 years of age listed for transplantation (1993 to 1999) were reviewed and patients who died waiting (Group I) were compared with survivors to transplant (Group II). RESULTS: Mean age of the patients (n = 46) was 8.3 +/- 8 years. Primary indications for transplant were ventricular dysfunction in 36 (78%), failed Fontan in 8 (18%) and severe hypoxemia in 2 (4%) patients. Thirty-two patients were Status 1 (70%), 14 were Status 2 and 5 patients were de-listed. Twenty-nine of the 41 patients that remained listed survived to transplant, 12 (29%) died waiting. Causes of death were sepsis in 2 and severe heart failure (HF) in 10 patients. Eight patients died with multi-system organ failure, including 3 on mechanical circulatory support. Mean time to death was 29 +/- 28 days and time to transplant was 94 +/- 176 days. Mean age at listing was younger in Group I (2.6 +/- 4 years) compared with Group II (9.1 +/- 7 years, p < 0.05). Mean HF duration was shorter in Group I (3.6 +/- 3.9 months) compared with Group II (25 +/- 33 months, p < 0.05). Fifty-day actuarial survival on the waiting list was lower in infants (38%) compared with older children (91%, p < 0.05). In contrast to the high mortality (71%) in infants with CHD, all infants with cardiomyopathy survived to transplant. CONCLUSIONS: Seventy-one percent of patients listed with CHD survived to transplant. Younger age at listing and rapid onset of HF were significant risk factors for pre-transplant mortality.     

Coronary atherosclerosis in cardiac transplant patients treated with total lymphoid irradiation.

BACKGROUND: Multiple episodes of rejection following cardiac transplantation have been associated with an increased incidence of coronary atherosclerosis. Total lymphoid irradiation (TLI) has been shown to be a successful treatment for persistent allograft rejection, but its effect on coronary arterial disease has yet to be evaluated. METHODS: From 1987 to 1999, 40 patients required TLI for persistent or recurrent allograft rejection following heart transplantation. Each patient's (Group 1, n = 31) post-transplant coronary angiograms were examined and compared with those of a control group (Group 2, (n = 32) matched for time of transplantation. Degree of coronary stenosis was assessed on a 6-point scale. All patients received induction therapy (rabbit anti-thymocyte globulin or OKT3) and standard triple immunosuppressive therapy. TLI (80 cGy x 10 fractions) was used for the treatment of recurrent or persistent rejection on the basis of clinical indications. Actuarial survival, number and treatment of rejection episodes, and severity of coronary artery disease were compared in each group. RESULTS: Recipient gender, age, race and cytomegalovirus (CMV) status at time of transplant, along with donor gender, CMV status and graft ischemia time, were similar in both groups. Group 1 donor age was younger than that of Group 2 (22.2 +/- 11.2 vs 31.5 +/- 13.6 years, p = 0.004), and the indication for surgery in Group 1 patients was more likely to be ischemic heart disease (15 of 31 vs 6 of 32, p = 0.02). Mean follow-up was 5.7 +/- 3.5 years in Group 1 vs 6.9 +/- 3.8 in Group 2 (p = NS). Group 1 had more rejection episodes (4.4 +/- 2.2 vs 2.3 +/- 2.0, p = 0.0002) and more steroid treatments (9.78 +/- 4.0 g vs 5.14 +/- 4.7 g, p < 0.0001), but less coronary artery disease compared with Group 2 (p = 0.035). CONCLUSIONS: Despite multiple episodes of rejection, patients treated with TLI after cardiac transplant appear to develop less coronary atherosclerosis than appropriately matched controls.     

Automatic internal cardioverter defibrillator: a bridge to heart transplantation

The automatic internal cardioverter defibrillator (AICD) is effective in preventing death in patients with malignant ventricular arrhythmias (VT/VF) refractory to medical therapy. Because of the long waiting period for heart transplantation and the high likelihood of sudden arrhythmic death in this population, this study was undertaken to assess the value of the AICD in patients awaiting heart transplantation who have refractory VT/VF. Fourteen patients awaiting heart transplantation who had a history of VT/VF underwent AICD implantation (10 extrapericardial and four intrapericardial) via median sternotomy. All patients survived the AICD implantation and have either had heart transplantation or await transplantation at present (1 to 24 months after AICD implantation). Twelve of these patients have received a mean of 10 AICD shocks (range, 0 to 32). One patient received 19 shocks in the 24-hour period before transplantation. Two patients have died of progressive heart failure. Five patients have gone on to successful transplantation, and seven patients await heart transplantation with a functioning AICD in place. In conclusion, the AICD represents a new "bridge" to heart transplantation that is well tolerated by these high-risk patients, avoids drug side effects, and is efficacious in aborting sudden death, thereby allowing them to undergo successful heart transplantation.     

Relevance of cardioverter defibrillators for the prevention of sudden cardiac death on the timing of heart transplantation

Information on the incidence of decompensation of chronic heart failure (CHF) in heart transplantation (HT) candidates eligible for prophylactic implantable cardioverter defibrillators (ICD) could provide insights into the influence of ICD on the timing for HT. METHODS: We investigated the prevalence of candidates satisfying SCD-HeFT and MADIT-II criteria for prophylactic ICD among patients (n = 317) with CHF referred to our tertiary center for HT. In addition to standard clinical and laboratory assessments, baseline evaluation included two-dimensional standard transthoracic echocardiogram and 12-lead electrocardiogram. RESULTS: At baseline, 19% of patients (n = 60) satisfied MADIT II criteria, and 58% (n = 185) fulfilled SCD-HeFT criteria. A total of 60% patients (n = 190) were eligible for prophylactic ICD implantation according to at least one set of criteria. Five-yr CHF decompensation-free survival was 68 +/- 4% in patients eligible for prophylactic ICD (p = 0.003), (RR 2.5, 95% CI 1.35-4.63). CONCLUSIONS: SCD-HeFT could imply a threefold rise in ICD eligibility in tertiary settings. As ICD-eligible patients would likely remain at high risk of progressive ventricular dysfunction, strict follow-up should be considered extremely important to allow a timely referral for HT.     

Clinical Indications for the Use of the "Poisk–IOM" Total Artificial Heart: The Experience of 13 Implantations in Humans

Success of total artificial heart (TAH) implantation as a temporary measure depends on three factors: proper patient selection, adequate surgical technique, and safe cardiac prostheses. From 1986 until March 1990, 237 patients with stagnant heart failure were examined. Sixty-one patients (27%) were put on a waiting list. Thirty-eight percent of them died awaiting transplantation. Thirteen TAH implantations were performed; nine patients who were not on a waiting list underwent TAH implantation by urgent indications. Four other patients underwent bridge TAH implantation after cardiac surgery. Our experience shows that the status of a patient before transplantation is a determinant factor and that it is possible to perform TAH implantation only in patients on a waiting list.     

Surgery for ventricular tachycardia of left ventricular origin: risk factors for success and long-term outcome.

OBJECTIVES: To review 26 consecutive patients with sustained monomorphic ventricular tachycardia (VT) of left ventricular origin, who underwent direct VT surgery. METHODS: Economic factors precluded the use of an implantable cardioverter defibrillator (ICD) in the majority of these patients, and the indication for surgery in 81% of patients was for failed medical drug therapy and 27% of patients had frequent or incessant life-threatening VT. The principles of direct VT surgery included intraoperative mapping, extended endocardial resection, cryoablation, left ventricular aneurysm repair by left ventricular remodelling and endoaneurysmorrhaphy, as well as coronary artery bypass grafting. RESULTS: Two patients with non-ischaemic VT were significantly younger (37.7 +/- 19.4 years, P = 0.03), had lower preoperative New York Heart Association class (P = 0.03), and had better left ventricular ejection fractions of 59.5 +/- 2.1% (P = 0.001) than the 24 ischaemic patients. No operative mortality or recurrence of VT occurred in this group. Ischaemic VT patients had an operative mortality of 8.3%; risk factors were concomitant valve surgery (P = 0.02), and perioperative intra-aortic balloon pump (P = 0.02). Surgery improved the left ventricular ejection fraction from 28.4 +/- 9.8% to 43.2 +/- 8.2% (P = 0.0001). Freedom from recurrence or inducibility of VT in operative survivors was 78.8 +/- 9.6% at 10 years; risk factors were arrhythmic focus remote to the left ventricular aneurysm (P = 0.015), and simple cryoablation or endocardial resection alone and not in combination (P = 0.003). Survival was 54.1 +/- 11.6% and 43.3 +/- 13.4% at 5 and 10 years, respectively, and there were no arrhythmic or sudden cardiac deaths. Patients with immediately life-threatening VT unsuitable for ICD implantation requiring urgent or emergent VT surgery had a 10-year survival of 22.2 +/- 13.9% compared to the more elective surgical group with a rate of 73.3 +/- 13.9% (P = 0.08). CONCLUSIONS: Direct VT surgery should remain an objective for symptomatic drug refractory VT of left ventricular origin.     

Tumor necrosis factor gene polymorphism and cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after cardiac transplantation. Tumor necrosis factor-alpha (TNF-alpha) may be a key factor in the development of CAV. Two bi-allelic polymorphisms associated with high TNF-alpha production have been identified in the TNF gene locus, TNFA1/2, at position -308 and TNFB1/2 at +252. We hypothesized that recipient TNFA2 and TNFB2 homozygosity is associated with the development of CAV after heart transplantation. METHODS: TNF gene polymorphisms were analyzed by multiplex fluorescent solid-phase mini-sequencing in 70 cardiac transplant recipients. Recipients homozygous for TNFA2 or TNFB2 (Group A, n = 29) were compared with recipients heterozygous or homozygous for TNFA1 and TNFB1 (Group B, n = 41). Coronary arteriography was performed annually or when indicated. Cumulative freedom from CAV and survival was calculated according to the Kaplan-Meier test. RESULTS: Mean follow-up was 3.8 +/- 0.3 years. In Group A, 11 of 29 recipients (38%) developed CAV compared with 9 of 41 (22%) in Group B (p = 0.12). Cumulative freedom from CAV at 3 years was 42% in Group A and 80% in Group B (p = 0.043). In Group A, 11 of 29 recipients (38%) died during follow-up compared with 4 of 41 (10%) in Group B (p = 0.006). Cumulative survival at 3 years was 72% in Group A and 93% in Group B (p = 0.003). CONCLUSIONS: The results suggest that TNFA2 and TNFB2 allele homozygosity is associated with cardiac allograft vasculopathy and mortality in heart transplant recipients.     

Effect of the TNF-alpha-promoter polymorphism on cardiac allograft rejection.

BACKGROUND: A polymorphism exists in the tumor necrosis factor alpha (TNF-alpha) promoter (position -308, G/A = TNFA1/TNFA2). The TNFA2 allele is associated with increased TNF-alpha production in vitro and has been reported to increase the risk of allograft rejection in pediatric recipients of cardiac transplantation. We examined the effect of the TNFA2 allele on the risk of allograft rejection in adult cardiac transplant recipients. METHODS: We prospectively analyzed 57 subjects (aged 54 +/- 11 years, 84% men, 49% ischemic) who underwent cardiac transplantation between October 1996 and July 2001. Patients were observed after transplantation (mean, 910 +/- 605 days) and the frequency of allograft rejection (biopsy Grade > or =2) in patients with the TNFA2 allele (Group A, n = 15) was compared with TNFA1 homozygotes (Group B, n = 42). Overall survival and time to rejection episodes also were compared between groups. RESULTS: The frequency of allograft rejection was similar between groups (Group A, 8/15 [56%]; Group B, 22/42 [52%]; p = 0.77). Time to rejection also was comparable (Group A, 17 +/- 11 days; Group B, 20 +/- 20 days, p = 0.74). Overall post-transplant survival was similar between groups (1- and 2-year percentage survival: Group A, 87% and 78%, Group B, 88% and 82%, p = 0.35). CONCLUSION: The TNFA2 allele was not associated with increased risk of rejection in adult cardiac transplant recipients. The impact of this polymorphism on overall post-transplant outcomes will require investigation in larger multicenter studies.     

QT dispersion predicts ventricular arrhythmia in pediatric cardiomyopathy patients referred for heart transplantation.

BACKGROUND: QT dispersion has been used in stratifying risk for sudden death in adults with dilated cardiomyopathy, but its role in the pediatric population has not been delineated. METHODS: We reviewed electrocardiograms in pediatric patients with dilated cardiomyopathy referred for heart transplantation, to evaluate the role of QT dispersion in predicting malignant arrhythmias in these patients. Three groups were defined: Group I (n = 13) had dilated cardiomyopathy and malignant ventricular arrhythmias, Group II (n = 13) had dilated cardiomyopathy with no ventricular arrhythmias and Group III (n = 30) consisted of normals. QT dispersion was defined as the duration of the shortest QT subtracted from that of the longest. In addition, the standard deviation of the QT intervals was calculated for each ECG, using 12 leads. RESULTS: QT dispersion was significantly prolonged in Group I (97 +/- 33 msec) compared to Group II (74 +/- 19 msec) and Group III (42 +/- 17 msec). QT standard deviation was also prolonged in Group I (30 +/- 11 msec) vs Group II (22 +/- 5 msec) and Group III (13 +/- 4 msec). Using a threshold value of 90 msec for QT dispersion or 25 msec for QT standard deviation, a sensitivity of 78% and a specificity of 70% was obtained for identifying patients who would subsequently develop ventricular arrhythmias. CONCLUSIONS: In pediatric heart transplant candidates with dilated cardiomyopathy, QT dispersion and QT standard deviation identify patients at higher risk for the development of malignant ventricular arrhythmia. This simple test can be helpful in the evaluation and management of these patients awaiting transplantation.     

Primary preventive cardioverter‐defibrillator implantation (Pro‐ICD) in patients awaiting heart transplantation. A prospective,randomized, controlled 12‐year follow‐up study

The aim of this study was to evaluate whether short‐term primary preventive cardioverter‐defibrillator (ICD) implantation as bridge to heart transplantation (HTX) provides any survival benefit. Thirty‐three patients awaiting HTX were randomized to either conventional therapy (control group) or primary preventive ICD implantation (ICD group). Fourteen patients had ischemic cardiomyopathy (ICM) and 19 patients had dilated cardiomyopathy (DCM). Sixteen patients were randomized to the ICD group and 17 patients were randomized to the control group. Twenty patients (61%) were transplanted after a waiting time of 10 ± 9 months. The remaining 13 patients (39%) were not transplanted because of clinical improvement (n = 5), cerebral hemorrhage (n = 3), or death (n = 5). On the waiting list, 3 ICD patients with DCM developed slow VTs without ICD intervention, two patients with ICM (6%) had fast VT terminated by the ICD, and no arrhythmic death was observed. After 11.9 years (median), 13 of 20 HTX patients (65%) and 5 of 13 non‐HTX patients (38%) were alive. Survivors had a higher LVEF (22 ± 6 vs. 17 ± 4%, P = 0.0092) and a better exercise capacity (75 ± 29 vs. 57 ± 24 Watt, P = 0.0566) at baseline as compared to nonsurvivors. This study may not support the general use of primary preventive ICDs as a short‐term bridge to heart transplantation.     

Bone mineral density in lung-transplant recipients before and after graft: prevention of lumbar spine post-transplantation-accelerated bone loss by pamidronate.

BACKGROUND: Lung-transplant recipients are at risk of osteoporosis. They may have low bone mass even before posttransplantation immunosuppressive therapy. We studied bone mineral density (BMD) before and after lung transplantation and compared the efficacy of antiresorptive therapies to calcium and vitamin D supplementation. METHODS: Areal BMD was assessed in 42 patients awaiting lung transplantation and measured again after surgery at 6 (n = 29), and at 12 months (n = 20). Nineteen patients received antiresorptive therapy (30 mg pamidronate IV every 3 months (n = 14), or hormonal replacement therapy (n = 5)), and 10 patients received only calcium and vitamin D supplements.RESULTS: Mean age- and gender-adjusted lumbar spine (LS) and femoral neck (FN) BMD was significantly decreased prior to transplantation (- 0.6 +/- 0.2, p< 0.01, and - 1.5 +/- 0.2 standard deviation, p < 0.001, respectively). At that time, 29% were osteoporotic (T-score < - 2.5 below the peak bone mass), while 55% were below - 1.0 T-score. Antiresorptive therapy decreased the rate of LS bone loss during the first 6 months and led to a significant increase of BMD at 1 year, with LS changes of + 0.2 +/- 0.1 vs - 0.4 +/- 0.1 Z-score in the calcium-vitamin D group (p< 0.002), and + 0.2 +/- 0.1 vs - 0.04 +/- 0.1 for FN (NS). One out of 20 patients experienced clinically evident fractures during antiresorptive therapy, and 3 out of 12 in the calcium-vitamin D group. CONCLUSION: A significant proportion of patients awaiting lung transplantation was osteoporotic or osteopenic. Antiresorptive therapy (pamidronate or hormone-replacement therapy (HRT)) prevented accelerated LS bone loss after graft.     

Survival of patients removed from the heart transplant waiting list

OBJECTIVE: End-stage heart failure has been associated with high mortality in the absence of transplantation. We evaluated the outcome of patients receiving optimal medical therapy who were removed from the cardiac transplant waiting list to determine survival and predictors of mortality. METHODS: We performed a retrospective review of 27 patients removed from the cardiac transplant waiting list from 1999 to 2001 at our institution. RESULTS: Mean age was 53 +/- 11 years; 16 of the patients were male. Status was IB in 3 cases and II in 24. Median time on the list was 32 months, and median follow-up was 2.9 years. Patients were removed from the transplant list because of either clinical improvement (group A, n = 18) or deterioration (group B, n = 9). In group A, 13 patients had improved functional status and 10 were in New York Heart Association class 1 or 2; 16 had improved echocardiographic left ventricular function. Survivals at 3 years were 100% in group A and 44% in group B (P <.01). CONCLUSION: Patients with end-stage heart failure who have clinical response to medical therapy have excellent 3-year survival. These data suggest the necessity of close evaluation of patients waiting for transplantation, with a low threshold for inactivation if persistent clinical improvement is observed.     

Heart transplantation in children after mechanical circulatory support with pulsatile pneumatic assist device.

BACKGROUND: Mechanical support with a pulsatile pneumatic ventricular assist device (VAD) is a complex rescue procedure performed in children with untreatable cardiogenic shock. Its impact on early and long-term survival after subsequent heart transplantation (HTx) remains to be determined. METHODS: We reviewed retrospectively the course of 95 children (median age, 8 years; range, 8 days-17 years; body weight, 24 kg; range, 3-110 kg) who underwent HTx. Group A, the elective-HTx group, consists of 33 children who were treated as outpatients before transplantation. Group B, the emergency-HTx group, has 44 children who were critically ill and hospitalized before transplantation but without ventricular assist devices, whereas Group C, the VAD-HTx group, consists of 18 children resuscitated and supported with pulsatile pneumatic VADs for a median time of 20 days. RESULTS: Overall actuarial survival after cardiac transplantation was 86% at 1 month, 82% at 1 year, and 78% at 5 years, without significant differences among the 3 sub-groups. Group A had the best long-term survival rate, 88% at 1 month, 88% at 1 year, and 80% at 5 years. Group B had a survival rate of 88% at 1 month, 82% at 1 year, and 79% at 5 years. Group C had a survival rate of 72% at 1 month, 72% at 1 year, and 72% at 5 years. We found no differences in neurologic outcome, acute cardiac rejection, or transplant failure. The survival rate was significantly better in the children with cardiomyopathy compared with those with congenital heart defects (p = 0.014). CONCLUSIONS: Bridging to HTx with a pulsatile pneumatic VAD is a safe procedure in pediatric patients. After HTx, overall survival of these children is similar to that of patients who were bridged with inotropes or who were awaiting heart transplantation electively.     

Multiglycosidorum tripterygii, a new immunosuppressant, supresses coronary arteriosclerosis after heart transplantation.

BACKGROUND: Graft coronary arteriosclerosis is the major limiting factor for long-term survival after heart transplantation. In this study, we investigate the effect of multiglycosidorum tripterygii on graft coronary arteriosclerosis and platelet-derived growth factor A mRNA expression of transplanted hearts. METHODS: Three groups of Lewis rats (n = 7/Group) underwent heterotopic heart transplantation from Wistar-King donors and were treated with cyclosporine A (10 mg/ kg/day) for 60 days (Group A) or with multiglycosidorum tripterygii (30 mg/kg/day) for 60 days (Group B) or with cyclosporine A for the first 30 days and followed by multiglycosidorum tripterygii for another 30 days (Group C). Histological evaluations of rejection and coronary arteriosclerosis, as well as Northern blot analysis on graft platelet-derived growth factor A mRNA expression were made 60 days after transplantation. RESULTS: Morphometric results indicated no significant difference in rejection among three groups. However, the extent of graft coronary arteriosclerosis in Group B (1.12 +/- 0.21) and Group C (1.41 +/- 0.19) was significantly less than that seen in Group A (1.72 +/- 0.18) (p < 0.01 andp < 0.05, respectively). Furthermore, the incidence of diseased vessels was significantly less in Group B (29.5% +/- 7.8%) and Group C (42% +/- 9.1%) compared with Group A (69.1% +/- 11%) (p < 0.01 and p < 0.05, respectively). The expression of platelet-derived growth factor A mRNA of cardiac allograft was also significantly suppressed in Group B (25.4 +/- 6.2) and Group C (39.8 +/- 9.4), when compared with Group A (62.2 +/- 12.9) (p < 0.01 and p < 0.05, respectively). CONCLUSION: Multiglycosidorum tripterygii is superior to cyclosporine in prevention and attenuation of graft coronary arteriosclerosis and this efficacy is probably associated with the depressed expression of graft platelet-derived growth factor A mRNA in the multiglycosidorum tripterygii-treated groups.     

Post-transplant survival after lowering fixed pulmonary hypertension using left ventricular assist devices.

OBJECTIVE: We have previously shown that fixed pulmonary hypertension in cardiac transplant candidates can be lowered using left ventricular assist devices (LVADs). The post-transplant survival of these patients is uncertain as pulmonary hypertension may reappear, possibly affecting post-transplant survival. MATERIALS AND METHODS: Between 01/2000 and 01/2005 a total of 26 cardiac transplant candidates (92% male; mean age 56.2 years) in whom fixed pulmonary hypertension was lowered by LVAD implantation (pulmonary vascular resistance (PVR) before implantation: 5.1+/-2.8wood units (WU); PVR before cardiac transplantation: 2.0+/-.9WU) underwent cardiac transplantation at our institution. These patients were age and sex matched with 52 cardiac transplant candidates without pulmonary hypertension undergoing cardiac transplantation during the same time period. Study endpoints were peri-transplant complications and long-term survival. Mean follow-up was 36+/-14 months. RESULTS: Peri-transplant mortality was 5% in patients after LVAD therapy and 7% in patients without prior LVAD therapy (p=.089). We observed 2 cases (4%) of acute right heart failure requiring mechanical support in patients without prior LVAD therapy. None of the patients with LVAD therapy developed peri-transplant right heart failure requiring mechanical support. Incidence of other peri-transplant complications was comparable between the two groups. Log-rank (p=.124) revealed comparable long-term survival between patients with (1 year: 85%, 2 year: 85%, 3 year: 85%) and without (1 year: 90%, 2 year 82%, 3 year prior 79%) prior LVAD therapy. CONCLUSION: LVAD therapy lowers fixed pulmonary hypertension in cardiac transplant candidates with fixed pulmonary hypertension. Thereafter, long-term post-transplant survival is comparable to cardiac transplant recipients without pulmonary hypertension.     

Home continuous positive inotropic infusion as a bridge to cardiac transplantation in patients with end-stage heart failure.

BACKGROUND: The clinical use of positive inotropic therapy at home in patients awaiting cardiac transplantation has not been reported since United Network for Organ Sharing (UNOS) regulations were changed to allow home infusions in Status 1B patients. METHODS: We observed 21 consecutive patients with UNOS 1B status during positive inotropic therapy at home. We used hemodynamic monitoring at the initiation of therapy to optimize dosing. We selected for home therapy patients with stable clinical status and improved functional capacity during inotropic treatment. Implantable cardioverter defibrillators were placed in all but 1 patient before discharge. RESULTS: Initial positive inotropic therapy included dobutamine in 12 patients (mean dose, 4.5 mcg/kg/min; range, 2.5-7.5 mcg/kg/min), milrinone in 8 patients (mean dose, 0.44 mcg/kg/min; range, 0.375-0.55 mcg/kg/min), and dopamine at a dose of 3 mcg/kg/min in 1 patient. Patients had improved functional capacity (New York Heart Association Class 3.7 +/- 0.1 to 2.4 +/- 0.2, p < 0.01), improved renal function (serum creatinine, 1.5 +/- 0.1 to 1.3 +/- 0.1, p < 0.01), improved resting hemodynamics, and decreased number of hospitalizations during positive inotropic infusion therapy when compared with pre-treatment baseline. Implantable cardioverter defibrillator discharges were infrequent (0.19 per 100 patient days of follow-up). Actuarial survival to transplantation at 6 and 12 months was 84%. CONCLUSIONS: Continuous positive inotropic therapy at home was safe and was associated with decreased health care costs in selected patients awaiting cardiac transplantation.     

Use of basiliximab and cyclosporine in heart transplant patients with pre-operative renal dysfunction.

BACKGROUND: The combined use of basiliximab and cyclosporine in heart transplantation is under investigation. In this study we sought to evaluate the safety and efficacy of basiliximab and delayed initiation of cyclosporine in patients with renal dysfunction undergoing heart transplantation. METHODS: Seven patients (Group A) with renal dysfunction (creatinine > or =200 micromol/liter) received induction therapy with basiliximab. Seven patients (Group B) with renal dysfunction comprised the control group and received induction therapy with rabbit anti-thymocyte serum. Cyclosporine was initiated 5 days post-transplant in Group A and within 5 days post-transplant in Group B. RESULTS: All patients were alive at the end of the 6-month follow-up. In Group A, mean pre-transplant creatinine was 243 +/- 48 micromol/liter, at 1 week post-transplant was 180 +/- 39 micromol/liter (p = 0.02), at 1 month was 166 +/- 57 micromol/liter (p = 0.019), at 3 months was 182 +/- 25 micromol/liter (p = 0.01) and at 6 months was 179 +/- 45 micromol/liter (p = 0.024). In Group B, mean pre-transplant creatinine was 242 +/- 41 micromol/liter, at 1 week was 140 +/- 35 micromol/liter (p = 0.0003), at 1 month was 143 +/- 38 mumol/liter (p = 0.0005), at 3 months was 138 +/- 37 micromol/liter (p = 0.0003) and at 6 months was 154 +/- 30 micromol/liter (p = 0.0006). There were no differences in renal dysfunction between both groups at 1 week (p = 0.069), 1 month (p = 0.39) or 6 months (p = 0.24) post-HT. Fewer episodes of cellular rejection were identified in Group B within the 6-month follow-up period. CONCLUSIONS: The use of induction therapy either with basiliximab or rabbit anti-thymocyte serum in patients with pre-operative renal dysfunction confers renal protection early and up to 6 months post-transplant. Delayed initiation of cyclosporine might be considered to provide additional renal protection.