The Stanford experience of heart transplantation over five decades.

AIMS: Since 1968, heart transplantation has become the definitive treatment for patients with end-stage heart failure. We aimed to summarize our experience in heart transplantation at Stanford University since the first transplantation performed over 50 years ago. METHODS AND RESULTS: From 6 January 1968 to 30 November 2020, 2671 patients presented to Stanford University for heart transplantation, of which 1958 were adult heart transplantations. Descriptive analyses were performed for patients in 1968-95 (n = 639). Stabilized inverse probability weighting was applied to compare patients in 1996-2006 (n = 356) vs. 2007-19 (n = 515). Follow-up data were updated through 2020. The primary endpoint was all-cause mortality. Prior to weighting, recipients in 2007-19 vs. those in 1996-2006 were older and had heavier burden of chronic diseases. After the application of stabilized inverse probability weighting, the distance organ travelled increased from 84.2 ± 111.1 miles to 159.3 ± 169.9 miles from 1996-2006 to 2007-19. Total allograft ischaemia time also increased over time (199.6 ± 52.7 vs. 225.3 ± 50.0 min). Patients in 2007-19 showed superior survival than those in 1996-2006 with a median survival of 12.1 vs. 11.1 years. CONCLUSION: In this half-century retrospective descriptive study from one of the largest heart transplant programmes in the USA, long-term survival after heart transplantation has improved over time despite increased recipient and donor age, worsening comorbidities, increased technical complexity, and prolonged total allograft ischaemia time. Further investigation is warranted to delineate factors associated with the excellent outcomes observed in this study.

Outcomes after heart retransplantation: A 50-year single-center experience.

OBJECTIVES: To evaluate outcomes after heart retransplantation. METHODS: From January 6, 1968, to June 2019, 123 patients (112 adult and 11 pediatric patients) underwent heart retransplantation, and 2092 received primary transplantation at our institution. Propensity-score matching was used to account for baseline differences between the retransplantation and the primary transplantation-only groups. Kaplan-Meier survival analyses were performed. The primary end point was all-cause mortality, and secondary end points were postoperative complications. RESULTS: Retransplantation recipient age was 39.6 ± 16.4 years, and donor age was 26.4 ± 11.2 years. Ninety-two recipients (74.8%) were male. Compared with recipients who only underwent primary heart transplantation, retransplantation recipients were more likely to have hypertension (44/73.3% vs 774/53.3%, P = .0022), hyperlipidemia (40/66.7% vs 447/30.7%, P < .0001), and require dialysis (7/11.7% vs 42/2.9%, P = .0025). The indications for heart retransplantation were cardiac allograft vasculopathy (32/80%), primary graft dysfunction (6/15%), and refractory acute rejection (2/5%). After matching, postoperative outcomes such as hospital length of stay, severe primary graft dysfunction requiring intra-aortic balloon pump or extracorporeal membrane oxygenation, cerebral vascular accident, respiratory failure, renal failure requiring dialysis, and infection were similar between the 2 groups. Matched median survival after retransplantation was 4.6 years compared with 6.5 years after primary heart transplantation (log-rank P = .36, stratified log-rank P = .0063). CONCLUSIONS: In this single-center cohort, the unadjusted long-term survival after heart retransplantation was inferior to that after primary heart transplantation, and short-term survival difference persisted after propensity-score matching. Heart retransplantation should be considered for select patients for optimal donor organ usage.

Type A Aortic Dissection-Experience Over 5 Decades: JACC Historical Breakthroughs in Perspective.

The Stanford classification of aortic dissection was described in 1970. The classification proposed that type A aortic dissection should be surgically repaired immediately, whereas type B aortic dissection can be treated medically. Since then, diagnostic tools and management of acute type A aortic dissection (ATAAD) have undergone substantial evolution. This paper evaluated historical changes of ATAAD repair at Stanford University since the establishment of the aortic dissection classification 50 years ago. The surgical approaches to the proximal and distal extent of the aorta, cerebral perfusion methods, and cannulation strategies were reviewed. Additional analyses using patients who underwent ATAAD repair at Stanford University from 1967 through December 2019 were performed to further illustrate the Stanford experience in the management of ATAAD. While technical complexity increased over time, post-operative survival continued to improve. Further investigation is warranted to delineate factors associated with the improved outcomes observed in this study.

Operative technique and pitfalls in donor heart procurement.

We describe a simple and reproducible donor heart procurement technique in sequential steps. A detailed understanding of procurement and organ preservation techniques should be an essential part of a heart transplant training program.

Influence of durable mechanical circulatory support and allosensitization on mortality after heart transplantation.

BACKGROUND: Allosensitization has been shown to negatively affect post-heart transplant (HTx) survival even with a negative crossmatch. Whether allosensitization related to mechanical circulatory support (MCS) is associated with worse post-HTx survival remains controversial. METHODS: Adult HTx recipients listed in the United Network for Organ Sharing database (July 2006-December 2012) were identified. Multivariate Cox regression assessed the effect of allosensitization on survival. Propensity matching was performed to compare patients who were and were not allosensitized. Kaplan-Meier survival analysis compared matched and unmatched patients in the MCS and medically managed cohorts. RESULTS: We identified 11,840 HTx recipients, of whom 4,167 had MCS. MCS was associated with allosensitization in multivariate logistic regression. Each different MCS device was associated with worse post-HTx survival in multivariate Cox regression. Allosensitization did not predict post-HTx mortality in MCS patients (hazard ratio, 1.07; 95% confidence interval, 0.89-1.28; p = 0.48. Among patients without MCS, allosensitization was associated with post-HTx mortality (hazard ratio, 1.19; 95% confidence interval, 1.03-1.39; p = 0.02). Kaplan-Meier analysis revealed equivalent survival in unmatched and matched cohorts when MCS patients who were allosensitized were compared with non-allosensitized MCS patients. Among non-MCS patients, allosensitization was associated with worse survival in unmatched and matched analysis. CONCLUSIONS: MCS was associated with allosensitization. For MCS patients, allosensitization did not independently predict worse post-HTx outcome. Among non-MCS patients, allosensitization was associated with worse post-HTx survival. Allosensitization appears to be a heterogeneous process influenced by presence of MCS.

Does profound hypothermic circulatory arrest improve survival in patients with acute type a aortic dissection?

OBJECTIVE: No evidence exists that profound hypothermic circulatory arrest (PHCA) improves survival or reduces the likelihood of distal aortic reoperation in patients with acute type A aortic dissection. METHODS: Records of 307 patients with acute type A aortic dissection from 1967 to 1999 were retrospectively reviewed. The influence of repair using PHCA (n=121) versus without PHCA (n=186) on death and freedom from distal aortic reoperation was analyzed using multivariable Cox regression models. Propensity score analysis identified a subset of 152 comparable patients in 3 quintiles (QIII-V) in which the effects of PHCA (n=113) versus no PHCA (n=39) were further compared. RESULTS: For all patients, 30-day, 1-year, and 5-year survival estimates were 81+/-2%, 74+/-3%, and 63+/-3% (+/-1 SE). Survival rates and actual freedom from distal aortic reoperation was not significantly different between treatment methods in the entire patient cohort nor in the matched patients in quintiles III-V. Treatment method was not associated with differences in early major complications, late survival, or distal aortic reoperation rates in the entire patient sample or in quintiles III-V. CONCLUSIONS: Aortic repair with or without circulatory arrest was associated with comparable early complications, survival, and distal aortic reoperation rates in patients with acute type A aortic dissection. Despite the lack of concrete evidence favoring the use of PHCA, it does no harm, and most of our group uses PHCA regularly because of its practical technical advantages and theoretical potential merit.

The impact of brain death on survival after heart transplantation: time is of the essence.

BACKGROUND: It has been suggested that the modality of brain death and time from brain death until harvest impact survival and rejection after heart transplantation. METHODS: Donor files from 475 adult heart-transplant recipients were examined. From these files, a total management time (time from incident leading to brain death until aortic cross clamp) was determined, and the cause of brain death was noted. Recipient characteristics, details of postoperative course, as well as survival were obtained from the Stanford University Medical Center Heart Transplantation Database. RESULTS: Two hundred and thirty (48.4%) donors sustained traumatic injuries, 112 (23.6%) suffered a subarachnoid hemorrhage, and 102 (21.4%) died of a gunshot wound to the head. The modality of brain death did not influence medium and long-term survival. A management time longer than 72 hours was associated with poorer outcome of the heart-transplant recipients. There were significantly more treated rejection episodes in recipients whose donor sustained traumatic injuries. CONCLUSION: Modality of brain death does not impact survival but appears to influence rejection. Increased management time is associated with adverse survival trends in heart-transplant recipients.

Long-term results of heart transplantation in patients older than 60 years.

BACKGROUND: Advanced age has been traditionally considered a relative contraindication for heart transplantation. Older patients are now considered as potential candidates for heart transplantation. The objective of this study was to evaluate the long-term results of heart transplantation in patients older than 60 years. METHODS: Between 1986 and 2001, 81 patients aged between 60 and 70 years (mean, 63 +/- 2 years) underwent heart transplantation. These patients were compared with 403 adult recipients younger than 60 years (mean, 47 +/- 11 years) who underwent transplantation during the same period. RESULTS: Thirty-day mortality was 6% (5/81) and 6% (25/403) in the older and younger patients, respectively (P = NS). Actuarial survival at 1, 5, and 10 years was 88% +/- 4% versus 83% +/- 2%, 75% +/- 5% versus 69% +/- 2%, and 50% +/- 9% versus 51% +/- 3% in the older and younger patients, respectively (P = NS). Older patients had significantly fewer rejection episodes (P =.003). Freedom from allograft coronary artery disease at 1, 5, and 10 years was 98% +/- 2% versus 92% +/- 2%, 85% +/- 6% versus 76% +/- 3%, and 81% +/- 7% versus 68% +/- 3% (P =.1). The incidences of infectious complication, cytomegalovirus infection, and posttransplant lymphoproliferative disorder were similar between the 2 groups, but older recipients were more likely to have a nonposttransplant lymphoproliferative disorder cancer (P =.002). Age at transplantation was not identified as an independent risk factor for early and late death. CONCLUSION: Heart transplantation in selected patients aged 60 years and older results in survival comparable with that of younger patients. Older patients have a lower risk of rejection but an increased risk of development of a nonposttransplant lymphoproliferative disorder cancer. Advanced age per se should not be considered as an exclusion criterion for transplantation.

Acute type A aortic dissection complicated by aortic regurgitation: composite valve graft versus separate valve graft versus conservative valve repair.

OBJECTIVE: To clarify the merits of various surgical approaches, we studied the outcome after composite valve graft versus separate valve and graft replacement versus conservative valve treatment with replacement of the ascending aorta in patients with acute type A aortic dissection complicated by aortic regurgitation. METHODS: Between 1967 and 1999, 123 patients (mean age 56 +/- 15 years) underwent composite valve graft replacement (n = 21), separate valve and graft replacement (n = 20), or conservative valve treatment (n = 82 [commissural resuspension in 46]); follow-up averaged 6.5 years (95% complete). RESULTS: The 30-day, 1-year, and 6-year survival estimates of 85% +/- 4%, 79% +/- 5%, and 69% +/- 5% (+/-1 standard error of mean), respectively, after conservative valve treatment were similar to 86% +/- 8%, 81% +/- 9%, and 65% +/- 16%, respectively, with composite valve graft replacement and better (but insignificantly so) than 70% +/- 10%, 70% +/- 10%, and 45% +/- 11%, respectively, with separate valve and graft replacement. The 6-year freedom from proximal reoperation was 95% +/- 3%, 89% +/- 10%, and 100% in conservative valve graft, separate valve and graft, and composite valve graft subgroups, respectively (P = not significant). Cox regression multivariable analysis identified that previous sternotomy (hazard ratio [or e(beta)] 95% confidence interval 1.4-10.9, P =.006), hypertension (0.99-2.9, P =.05), cardiac tamponade (1.1-4.0, P =.03), and stroke (1.7-7.0, P =.001) increased the hazard of death. No factors predicting a higher likelihood of late proximal reoperation were identified. CONCLUSIONS: In patients with acute type A aortic dissection and aortic regurgitation, there was no significant difference in overall survival or reoperation rates among these surgical approaches. We try to save the valve whenever possible unless the aortic root is pathologically dilated (eg, Marfan syndrome or annuloaortic ectasia) or destroyed by the dissection process, when composite valve graft or valve-sparing aortic root replacement is indicated.

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.

Heart transplant graft survival is improved after a reduction in panel reactive antibody activity.

BACKGROUND: Allosensitization in potential orthotopic heart transplant recipients is evaluated with the panel reactive antibody assay. Sensitized patients have prolonged wait times and increased waitlist and post-transplant mortality. Although low panel reactive antibody activity at the time of orthotopic heart transplantation is associated with improved outcomes, literature regarding the survival benefit of a panel reactive antibody reduction in the sensitized orthotopic heart transplant recipient remains limited. METHODS: Adult orthotopic heart transplant recipients listed in the United Network for Organ Sharing database (October 1, 1987, to June 29, 2004) were stratified by peak panel reactive antibody activity and whether a substantial decline from peak to most recent panel reactive antibody activity occurred before transplant. Propensity matching adjusted for differences in recipient and donor characteristics. Graft survival was assessed with Kaplan-Meier analysis. Cox proportional hazards regression determined predictors of graft survival. RESULTS: Pretransplant characteristics differed between sensitized patients who had a substantial decline in panel reactive antibody activity and those who did not. Propensity matching compensated for these differences. Kaplan-Meier survival analysis of matched groups showed that the median graft survival was 120 months in patients with a significant panel reactive antibody reduction and 103 months in patients with a trivial reduction (P = .007, log-rank). In Cox proportional hazards modeling, a significant reduction in panel reactive antibody activity had an independent protective effect on graft survival (hazard ratio, 0.88; confidence interval, 0.80-0.96; P = .006). CONCLUSIONS: Sensitized patients who had a substantial reduction in panel reactive antibody activity had an associated decline in the incidence of graft failure compared with those without a panel reactive antibody activity reduction. These results support efforts to reduce panel reactive antibody activity before orthotopic heart transplantation in patients with high panel reactive antibody activity.

Ventricular assist devices: history, patient selection, and timing of therapy.

Timing of therapy and selection of patients in the use of ventricular assist devices (VADs) can be difficult. In general, consideration for VAD implantation is appropriate in patients with endstage heart failure who are failing optimal medical therapy and in whom no alternative traditional surgical treatment options are available. However, identifying when a particular patient has reached this point is not always straightforward. There are a broad range of medical and surgical therapies for patients with overt heart failure, and this armamentarium is constantly expanding. The risks, benefits, and expected outcomes with VAD therapy have also undergone dramatic changes over the last decade. Advances in technology have led to a proliferation of newer generation devices that are smaller, lighter, easier to implant, and more reliable than previous generation devices. This, in turn, has led to a markedly improved risk-benefit ratio, with increased durability and reduced morbidity. The indications for the implantation of ventricular assist devices have also evolved over the last several years, and specific patient presentations and goals of therapy have led to specific indications. Device therapy has traditionally been classified as bridge to recovery, bridge to transplantation, and destination therapy. However, such designations may not be well defined at the time of implantation, and recovery and response following initiation of VAD support may allow patients to change from one classification to another. The current data regarding indications and timing of device implantation are reviewed.