Four decades of progress in heart-lung transplantation: Two hundred seventy-one cases at a single institution.

OBJECTIVE: The objective of this study is to evaluate survival for combined heart-lung transplant (HLTx) recipients across 4 decades at a single institution. We aim to summarize our contemporary practice based on more than 271 HLTx procedures over 40 years. METHODS: Data were collected from a departmental database and the United Network for Organ Sharing. Recipients younger than age 18 years, those undergoing redo HLTx, or triple-organ system transplantation were excluded, leaving 271 patients for analysis. The pioneering era was defined by date of transplant between 1981 and 2000 (n = 155), and the modern era between 2001 and 2022 (n = 116). Survival analysis was performed using cardinality matching of populations based on donor and recipient age, donor and recipient sex, ischemic time, and sex matching. RESULTS: Between 1981 and 2022, 271 HLTx were performed at a single institution. Recipients in the modern era were older (age 42 vs 34 y; P < .001) and had shorter waitlist times (78 vs 234 days; P < .001). Allografts from female donors were more common in the modern era (59% vs 39%; P = .002). In the matched survival analysis, 30-day survival (97% vs 84%; P = .005), 1-year survival (89% vs 77%; P = .041), and 10-year survival (53% vs 26%; P = .012) significantly improved in the modern era relative to the pioneering era, respectively. CONCLUSIONS: Long-term survival in HLTx is achievable with institutional experience and may continue to improve in the coming decades. Advances in mechanical circulatory support, improved maintenance immunosuppression, and early recognition and management of acute complications such as primary graft dysfunction and acute rejection have dramatically improved the prognosis for recipients of HLTx in our contemporary institutional experience.

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.

Combined Heart Lung Transplantation: An Updated Review of the Current Literature.

Heart lung transplantation is a viable treatment option for patients with many end-stage heart and lung pathologies. However, given the complex nature of the procedure, it is imperative that patients are selected appropriately, and the clinician is aware of the many unique aspects in management of this population. This review seeks to describe updated organ selection policies, perioperative and postoperative management strategies, monitoring of graft function, and clinical outcomes for patients after combined heart-lung transplantation in the current era.

Changes in Risk Profile Over Time in the Population of a Pediatric Heart Transplant Program.

BACKGROUND: Single-center data on pediatric heart transplantation spanning long time frames is sparse. We attempted to analyze how risk profile and pediatric heart transplant survival outcomes at a large center changed over time. METHODS: We divided 320 pediatric heart transplants done at Stanford University between 1974 and 2014 into three groups by era: the first 20 years (95 transplants), the subsequent 10 years (87 transplants), and the most recent 10 years (138 transplants). Differences in age at transplant, indication, mechanical support, and survival were analyzed. RESULTS: Follow-up was 100% complete. Average age at time of transplantation was 10.4 years, 11.9 years, and 5.6 years in eras 1, 2, and 3, respectively. The percentage of infants who received transplants by era was 21%, 7%, and 18%, respectively. The indication of end-stage congenital heart disease vs cardiomyopathy was 24%, 22%, and 49%, respectively. Only 1 patient (1%) was on mechanical support at transplant in era 1 compared with 15% in era 2 and 30% in era 3. Overall survival was 72% at 5 years and 57% at 10 years. Long-term survival increased significantly with each subsequent era. Patients with cardiomyopathy generally had a survival advantage over those with congenital heart disease. CONCLUSIONS: The risk profile of pediatric transplant patients in our institution has increased over time. In the last 10 years, median age has decreased and ventricular assist device support has increased dramatically. Transplantation for end-stage congenital heart disease is increasingly common. Despite this, long-term survival has significantly and consistently improved.

Elevated pretransplant pulmonary vascular resistance index does not predict mortality after isolated orthotopic heart transplantation in children: A retrospective analysis of the UNOS database.

OHT is the definitive therapy in end-stage heart failure. Elevated PVRI is considered a relative contraindication to isolated OHT; this assumption is re-evaluated using data from the UNOS database. A retrospective review of de-identified data from the UNOS dataset was performed. There were 1943 pediatric OHT recipients between 10/87 and 12/11 with sufficient data for analysis. Cox regression was performed to examine the effect of baseline characteristics on post-transplant survival. Patients were propensity matched, and Kaplan-Meier survival analysis was performed comparing cohorts of patients using thresholds of 6 and 9 WU × m(2) . PVRI was not a significant predictor of post-transplant outcomes in either univariate or multivariate Cox regression. Kaplan-Meier analysis revealed no difference in survival between both unmatched and propensity-matched OHT recipients. In conclusion, elevated PVRI was not associated with post-transplant mortality in pediatric OHT recipients. A prospective study assessing the current use of PVRI ≥6 as a threshold to contraindicate isolated OHT should be undertaken. Removing this potentially unnecessary restriction on transplant candidacy may make this life-saving therapy available to a greater number of patients.

Single- vs double-lung transplantation in patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis since the implementation of lung allocation based on medical need.

IMPORTANCE: Outcomes of single- and double-lung transplantation have not been rigorously assessed since the allocation of donor lungs according to medical need as quantified by the Lung Allocation Score, which began in 2005. OBJECTIVE: To compare outcomes in single- and double-lung transplant recipients since the Lung Allocation Score was implemented. DESIGN, SETTING, AND PARTICIPANTS: In this exploratory analysis, adults with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) who underwent lung transplantation in the United States between May 4, 2005, and December 31, 2012, were identified in the United Network for Organ Sharing thoracic registry, with follow-up to December 31, 2012. Posttransplantation graft survival was assessed with Kaplan-Meier analysis. Propensity scores were used to control for treatment selection bias. A multivariable flexible parametric prognostic model was used to characterize the time-varying hazard associated with single- vs double-lung transplantation. EXPOSURE: Single- or double-lung transplantation. MAIN OUTCOMES AND MEASURES: Composite of posttransplant death and graft failure (retransplantation). RESULTS: Patients with IPF (n = 4134, of whom 2010 underwent single-lung and 2124 underwent double-lung transplantation) or COPD (n = 3174, of whom 1299 underwent single-lung and 1875 underwent double-lung transplantation) were identified as having undergone lung transplantation since May 2005. Median follow-up was 23.5 months. Of the patients with IPF, 1380 (33.4%) died and 115 (2.8%) underwent retransplantation; of the patients with COPD, 1138 (34.0%) died and 59 (1.9%) underwent retransplantation. After confounders were controlled for with propensity score analysis, double-lung transplants were associated with better graft survival in patients with IPF (adjusted median survival, 65.2 months [interquartile range {IQR}, 21.4-91.3 months] vs 50.4 months [IQR, 17.0-87.5 months]; P < .001) but not in patients with COPD (adjusted median survival, 67.7 months [IQR, 25.2-89.6 months] vs 64.0 months [IQR, 25.2-88.7 months]; P = .23). The interaction between diagnosis type (COPD or IPF) and graft failure was significant (P = .049). Double-lung transplants had a time-varying association with graft survival; a decreased instantaneous late hazard for death or graft failure among patients with IPF was noted at 1 year and persisted at 5 years postoperatively (instantaneous hazard at 5 years, hazard ratio, 0.67 [95% CI, 0.52-0.84] in patients with IPF and 0.89 [95% CI, 0.71-1.13] in patients with COPD). CONCLUSIONS AND RELEVANCE: In an exploratory analysis of registry data since implementation of a medical need-based lung allocation system, double-lung transplantation was associated with better graft survival than single-lung transplantation in patients with IPF. In patients with COPD, there was no survival difference between single- and double-lung transplant recipients at 5 years.

One Hundred Years of History at Stanford University: Thoracic and Cardiovascular Surgery.

The history of thoracic and cardiovascular surgery at Stanford spans a century long period, beginning not long after the founding of Stanford University. Pioneering Stanford surgeons have made landmark discoveries and innovations in pulmonary, transplantation, thoracic aortic, mechanical circulatory support, minimally invasive, valvular, and congenital heart surgery. Fundamental research formed the foundation underlying these and many other advances. Educating and training the subsequent leaders of cardiothoracic surgery has throughout this century-long history constituted a mission of the highest merit.

Long-term outcomes of septal reduction for obstructive hypertrophic cardiomyopathy.

BACKGROUND: Surgical myectomy and alcohol septal ablation (ASA) aim to decrease left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM). Outcome of myectomy beyond 10 years has rarely been described. We describe 20 years of follow-up of surgical myectomy and 5 years of follow-up for ASA performed for obstructive HCM. METHODS: We studied 171 patients who underwent myectomy for symptomatic LVOT obstruction between 1972 and 2006. In addition, we studied 52 patients who underwent ASA for the same indication and who declined surgery. Follow-up of New York Heart Association (NYHA) functional class, echocardiographic data, and vital status were obtained from patient records. Mortality rates were compared with expected mortality rates of age- and sex-matched populations. RESULTS: Surgical myectomy improved NYHA class (2.74±0.65 to 1.54±0.74, p<0.001), reduced resting gradient (67.4±43.4mmHg to 11.2±16.4mmHg, p<0.001), and inducible LVOT gradient (98.1±34.7mmHg to 33.6±34.9mmHg, p<0.001). Similarly, ASA improved functional class (2.99±0.35 to 1.5±0.74, p<0.001), resting gradient (67.1±26.9mmHg to 23.9±29.4mmHg, p<0.001) and provoked gradient (104.4±34.9mmHg to 35.5±38.6mmHg, p<0.001). Survival after myectomy at 5, 10, 15, and 20 years of follow-up was 92.9%, 81.1%, 68.9%, and 47.5%, respectively. Of note, long-term survival after myectomy was lower than for the general population [standardized mortality ratio (SMR)=1.40, p<0.005], but still compared favorably with historical data from non-operated HCM patients. Survival after ASA at 2 and 5 years was 97.8% and 94.7%, respectively. Short-term (5 year) survival after ASA (SMR=0.61, p=0.48) was comparable to that of the general population. CONCLUSION: Long-term follow-up of septal reduction strategies in obstructive HCM reveals that surgical myectomy and ASA are effective for symptom relief and LVOT gradient reduction and are associated with favorable survival. While overall prognosis for the community HCM population is similar to the general population, the need for surgical myectomy may identify a sub-group with poorer long-term prognosis. We await long-term outcomes of more extensive myectomy approaches adopted in the past 10 years at major institutions.

Adoption and effectiveness of internal mammary artery grafting in coronary artery bypass surgery among Medicare beneficiaries.

OBJECTIVES: The aim of this study was to assess the pattern of the adoption of internal mammary artery (IMA) grafting in the United States, test its association with clinical outcomes, and assess whether its effectiveness differs in key clinical subgroups. BACKGROUND: The effect of IMA grafting on major clinical outcomes has never been tested in a large randomized trial, yet it is now a quality standard for coronary artery bypass graft (CABG) surgery. METHODS: We identified Medicare beneficiaries ≥66 years of age who underwent isolated multivessel CABG between 1988 and 2008, and we documented patterns of IMA use over time. We used a multivariable propensity score to match patients with and without an IMA and compared rates of death, myocardial infarction (MI), and repeat revascularization. We tested for variations in IMA effectiveness with treatment × covariate interaction tests. RESULTS: The IMA use in CABG rose slowly from 31% in 1988 to 91% in 2008, with persistent wide geographic variations. Among 60,896 propensity score-matched patients over a median 6.8-year follow-up, IMA use was associated with lower all-cause mortality (adjusted hazard ratio: 0.77, p < 0.001), lower death or MI (adjusted hazard ratio: 0.77, p < 0.001), and fewer repeat revascularizations over 5 years (8% vs. 9%, p < 0.001). The association between IMA use and lower mortality was significantly weaker (p ≤ 0.008) for older patients, women, and patients with diabetes or peripheral arterial disease. CONCLUSIONS: Internal mammary artery grafting was adopted slowly and still shows substantial geographic variation. IMA use is associated with lower rates of death, MI, and repeat coronary revascularization.

Transplantation for idiopathic pulmonary arterial hypertension: improvement in the lung allocation score era.

BACKGROUND: Lung transplantation and heart-lung transplantation represent surgical options for treatment of medically refractory idiopathic pulmonary arterial hypertension. The effect of the lung allocation score on wait-list and transplantation outcomes in patients with idiopathic pulmonary arterial hypertension is poorly described. METHODS AND RESULTS: Adults diagnosed with idiopathic pulmonary arterial hypertension and listed for transplantation in the 80 months before and after the lung allocation score algorithm was implemented (n=1430) were identified in the United Network for Organ Sharing thoracic registry. Patients were stratified by organ listed and pre- and post-lung allocation score era. The cumulative incidences of transplantation and mortality for wait-listed patients in both eras were appraised with competing outcomes analysis. Posttransplantation survival was assessed with the Kaplan-Meier method. These analyses were repeated in propensity-matched subgroups. Cox proportional hazards analysis evaluated the effect of prelisting and pretransplantation characteristics on mortality. We found that patients in the post-lung allocation score era had significantly worse comorbidities; nevertheless, both lung transplantation and heart-lung transplantation candidates in this era enjoyed lower wait-list mortality and a higher incidence of transplantation in unmatched and propensity-matched analyses. On multivariable analysis, heart-lung transplantation and double-lung transplantation were associated with improved survival from the time of wait-listing, as was being listed at a medium- to high-volume institution. Donor/recipient sex matching predicted posttransplantation survival. CONCLUSIONS: The incidence of transplantation has increased while wait-list mortality has decreased in patients with idiopathic pulmonary arterial hypertension wait-listed for transplantation in the post-lung allocation score era. Both heart-lung transplantation and double-lung transplantation are predictive of survival in transplantation candidates with idiopathic pulmonary arterial hypertension, as is being listed at a medium- to high-volume institution. Donor/recipient sex matching is associated with better posttransplantation survival.

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.

Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)-defined morbidity and mortality associated with pediatric ventricular assist device support at a single US center: the Stanford experience.

BACKGROUND: The use of ventricular assist devices (VADs) to bridge pediatric patients to heart transplantation has increased dramatically over the last 15 years. In this report, we present the largest US single-center report of pediatric VAD use to date. We present detailed descriptions of morbidity and mortality associated with VAD support, using standard Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) criteria for pediatrics to facilitate the comparison of these results to other studies. METHODS AND RESULTS: We retrospectively identified 25 patients younger than 18 years with 27 episodes of mechanical circulatory support using VADs as bridge to heart transplantation from January 1998 to December 2007. Survival to transplant for the entire cohort was 74%. The most common major morbidities, as defined by INTERMACS criteria for a pediatric population, were respiratory failure, major localized infections, major bleeding events, hepatic dysfunction, and right heart failure. Major neurological events occurred in 48% of the study population. The median time to the first occurrence of an adverse event was less than 14 days for respiratory failure, right heart failure, major localized infection, and major bleeding. Patients who died before transplantation had significantly more adverse events per day of support than did those who were successfully transplanted. Episodes of major bleeding, tamponade, acute renal failure, respiratory failure, and right heart failure were all associated with increased risk of mortality. CONCLUSIONS: INTERMACS criteria can be successfully used to analyze pediatric VAD outcomes. These data serve as a baseline for future studies of VAD support in children and indicate good survival rates but considerable morbidity.

Case report: a thrombus in the venous reservoir while using bivalirudin in a patient with heparin-induced thrombocytopenia undergoing heart transplantation.

Direct thrombin inhibitors are heparin alternatives for anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. We report a case of a large thrombus forming in the venous reservoir while using bivalirudin. We suggest that blood stasis associated with the full venous reservoir maintained in this case led to formation of a large thrombus at the top of the venous canister. Furthermore, activated clotting times may not accurately reflect the magnitude of anticoagulation when using direct thrombin inhibitors.

Review of heart-lung transplantation at Stanford.

Long-term survival after heart-lung transplantation was first achieved in 1981 at Stanford and a total of 217 heart-lung transplantations had been performed by June 2008. This review summarizes Stanford's cumulative experience with heart-lung transplantation, demonstrates the progress that has been made, and discusses past and persistent problems. Diagnostic tools and treatment options for infectious diseases and rejection have changed and patient survival markedly improved over the almost three decades. Eight patients lived longer than 20 years. Further options to treat infections and strategies to control bronchiolitis obliterans syndrome, the main causes of early and long-term mortality, respectively, are required to achieve routine long-term survival.

Alternative technique for salvage of donor lungs with insufficient atrial cuffs.

Inadequate left atrial cuff surrounding donor pulmonary veins may present a technical challenge for successful lung transplantation. A simple technique for construction of venous anastomoses during lung transplantation when donor atrial cuff is lacking involves circumferential incorporation of surrounding donor pericardium into the anastomosis without directly suturing or augmenting donor venous structures.

Heart-lung transplantation in situs inversus totalis.

Situs inversus totalis is a condition with left-to-right reversal of the viscera combined with dextrocardia. It has long been regarded a contraindication for thoracic transplantation. Reconstruction of the mirror-image systemic venous pathways to accommodate normal donor organs remains the main surgical challenge. Here we present our simplified surgical technique for combined heart-lung transplantation and provide a concise review of the literature.