Sirolimus-Based Immunosuppression Is Associated with Decreased Incidence of Post-Transplant Lymphoproliferative Disorder after Heart Transplantation: A Double-Center Study.

Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce proliferation of lymphoid cells; thus, their use for immunosuppression after heart transplantation (HT) may reduce post-transplant lymphoproliferative disorder (PTLD) risk. This study sought to investigate whether the sirolimus (SRL)-based immunosuppression regimen is associated with a decreased risk of PTLD compared with the calcineurin inhibitor (CNI)-based regimen in HT recipients. We retrospectively analyzed 590 patients who received HTs at two large institutions between 1 June 1988 and 31 December 2014. Cox proportional-hazard modeling was used to examine the association between type of primary immunosuppression and PTLD after adjustment for potential confounders, including Epstein-Barr virus (EBV) status, type of induction therapy, and rejection. Conversion from CNI to SRL as primary immunosuppression occurred in 249 patients (42.2%). During a median follow-up of 6.3 years, 30 patients developed PTLD (5.1%). In a univariate analysis, EBV mismatch was strongly associated with increased risk of PTLD (HR 10.0, 95% CI: 3.8-26.6; p < 0.001), and conversion to SRL was found to be protective against development of PTLD (HR 0.19, 95% CI: 0.04-0.80; p = 0.02). In a multivariable model and after adjusting for EBV mismatch, conversion to SRL remained protective against risk of PTLD compared with continued CNI use (HR 0.12, 95% CI: 0.03-0.55; p = 0.006). In conclusion, SRL-based immunosuppression is associated with lower incidence of PTLD after HT. These findings provide evidence of a benefit from conversion to SRL as maintenance therapy for mitigating the risk of PTLD, particularly among patients at high PTLD risk.

Heart-After-Liver Transplantation Attenuates Rejection of Cardiac Allografts in Sensitized Patients.

BACKGROUND: In patients undergoing heart transplantation, significant allosensitization limits access to organs, resulting in longer wait times and high waitlist mortality. Current desensitization strategies are limited in enabling successful transplantation. OBJECTIVES: The purpose of this study was to describe the cumulative experience of combined heart-liver transplantation using a novel heart-after-liver transplant (HALT) protocol resulting in profound immunologic protection. METHODS: Reported are the results of a clinical protocol that was instituted to transplant highly sensitized patients requiring combined heart and liver transplantation at a single institution. Patients were dual-organ listed with perceived elevated risk of rejection or markedly prolonged waitlist time due to high levels of allo-antibodies. Detailed immunological data and long-term patient and graft outcomes were obtained. RESULTS: A total of 7 patients (age 43 ± 7 years, 86% women) with high allosensitization (median calculated panel reactive antibody = 77%) underwent HALT. All had significant, unacceptable donor specific antibodies (DSA) (>4,000 mean fluorescence antibody). Prospective pre-operative flow cytometric T-cell crossmatch was positive in all, and B-cell crossmatch was positive in 5 of 7. After HALT, retrospective crossmatch (B- and T-cell) became negative in all. DSA fell dramatically; at last follow-up, all pre-formed or de novo DSA levels were insignificant at <2,000 mean fluorescence antibody. No patients experienced >1R rejection over a median follow-up of 48 months (interquartile range: 25 to 68 months). There was 1 death due to metastatic cancer and no significant graft dysfunction. CONCLUSIONS: A heart-after-liver transplantation protocol enables successful transplantation via near-elimination of DSA and is effective in preventing adverse immunological outcomes in highly sensitized patients listed for combined heart-liver transplantation.

Effects of mTOR inhibitor-related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients.

We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk.

Predictors and Clinical Outcomes of Vasoplegia in Patients Bridged to Heart Transplantation With Continuous-Flow Left Ventricular Assist Devices.

Background The presence of a durable left ventricular assist device (LVAD) is associated with increased risk of vasoplegia in the early postoperative period following heart transplantation (HT). However, preoperative predictors of vasoplegia and its impact on survival after HT are unknown. We sought to examine predictors and outcomes of patients who develop vasoplegia after HT following bridging therapy with an LVAD. Methods and Results We identified 94 patients who underwent HT after bridging with continuous-flow LVAD from 2008 to 2018 at a single institution. Vasoplegia was defined as persistent low vascular resistance requiring ≥2 intravenous vasopressors within 48 hours after HT for >24 hours to maintain mean arterial pressure >70 mm Hg. Overall, 44 patients (46.8%) developed vasoplegia after HT. Patients with and without vasoplegia had similar preoperative LVAD, echocardiographic, and hemodynamic parameters. Patients with vasoplegia were significantly older; had longer LVAD support, higher preoperative creatinine, longer cardiopulmonary bypass time, and higher Charlson comorbidity index; and more often underwent combined organ transplantation. In a multivariate logistic regression model, older age (odds ratio: 1.08 per year; P=0.010), longer LVAD support (odds ratio: 1.06 per month; P=0.007), higher creatinine (odds ratio: 3.9 per 1 mg/dL; P=0.039), and longer cardiopulmonary bypass time (odds ratio: 1.83 per hour; P=0.044) were independent predictors of vasoplegia. After mean follow-up of 4.0 years after HT, vasoplegia was associated with increased risk of all-cause mortality (hazard ratio: 5.20; 95% CI, 1.71-19.28; P=0.003). Conclusions Older age, longer LVAD support, impaired renal function, and prolonged intraoperative CPB time are independent predictors of vasoplegia in patients undergoing HT after LVAD bridging. Vasoplegia is associated with worse prognosis; therefore, detailed assessment of these predictors can be clinically important.

Incidence of Malignancies in Patients Treated With Sirolimus Following Heart Transplantation.

BACKGROUND: Malignancy is a major cause of late post-heart transplantation (HT) mortality. Sirolimus (SRL) exerts antiproliferative properties and its long-term use in HT as primary immunosuppression (IS) is associated with decreased mortality risk that is not fully explained by attenuation of cardiac allograft vasculopathy progression. OBJECTIVES: This study sought to examine whether conversion from calcineurin inhibitor (CNI)-based to SRL-based IS was associated with decreased risk of malignancy post-HT. METHODS: Overall, 523 patients underwent HT between 1994 and 2016 at a single institution. The main outcomes included incidence of overall de novo malignancies (excluding non-melanoma skin cancers [NMSCs]), post-transplantation lymphoproliferative disorders (PTLD), and first and subsequent primary occurrences of NMSC post-HT. RESULTS: The study identified 307 patients on SRL-based and 216 on CNI-based maintenance IS. Over a median follow-up of 10 years after HT, overall de novo malignancies (non-NMSC) occurred in 31% of CNI patients and in 13% of SRL patients (adjusted hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.18 to 0.62; p < 0.001). The incidence of the first NMSC was similar in the SRL and CNI groups (HR: 0.92; 95% CI: 0.66 to 1.28; p = 0.62). However, conversion to SRL was significantly associated with a decreased risk of subsequent primary occurrences of NMSC compared with that of CNI (adjusted HR: 0.44; 95% CI: 0.28 to 0.69; p < 0.001). The adjusted PTLD risk was significantly decreased in the SRL group (HR: 0.13; 95% CI: 0.03 to 0.59; p = 0.009). Late survival post-HT was markedly decreased in patients who developed non-NMSC, PTLD, or non-PTLD compared with patients who did not develop these malignancies, whereas NMSC had no significant effect on survival. CONCLUSIONS: Conversion to SRL was associated with a decreased risk of all de novo malignancies, PTLD, and subsequent primary occurrences of NMSC after HT. These findings provided further explanation of the late survival benefit with long-term SRL use.

Timing of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor initiation and allograft vasculopathy progression and outcomes in heart transplant recipients.

AIMS: Early studies from the 1990s have shown that statins improve survival and attenuate cardiac allograft vasculopathy (CAV). However, little contemporary data are available on the incremental benefit of statins with the current use of new-generation immunosuppressive agents and the use of coronary intravascular ultrasound for assessment of CAV. We sought to investigate the effect of early statin (ES) as compared with late statin (LS) initiation after heart transplantation (HT) on long-term CAV progression and clinical outcomes in a large contemporary HT cohort. METHODS AND RESULTS: We analysed a cohort of 409 adult HT recipients. CAV progression was assessed by serial coronary intravascular ultrasound volumetric measurements of the differences between baseline and last follow-up plaque volume (PV) and plaque index (PV/vessel volume ratio). CAV progression and clinical outcomes were compared between the ES (<2 years after HT) and the LS (>2 years after HT) groups. During a median follow-up of 8.2 years, ES resulted in significantly lower change (Δ) of plaque index (+3.8% ± 1.7% vs. +8.2% ± 3.6%; P = 0.0008) and PV (+0.8 ± 0.3 vs. +1.9 ± 1.2; P = 0.045) compared with LS group. In a Cox proportional hazards regression model and after adjustment for baseline characteristics, ES was associated with a 52% decreased risk of CAV-associated events (hazard ratio 0.48, 95% confidence interval: 0.27-0.91; P = 0.025) and a 42% decreased risk of the composite endpoint of all-cause mortality and CAV-associated events (hazard ratio 0.58, 95% confidence interval: 0.38-0.91; P = 0.019). CONCLUSIONS: Early initiation of statin therapy after HT results in attenuated CAV progression as well as in decreased CAV-related events and mortality.

Outcomes After Cardiac Transplant for Wild Type Transthyretin Amyloidosis.

BACKGROUND: The true prevalence of heart failure due to wild type transthyretin amyloidosis (ATTRwt) is likely underestimated. There is a paucity of data with regard to the management of ATTRwt-related advanced heart failure and the natural history of extracardiac ATTRwt. METHODS: We conducted a retrospective cohort study of patients undergoing cardiac transplant (HTx) for ATTRwt at a single institution. Comprehensive clinical data, including baseline hemodynamic and echocardiographic characteristics, and posttransplant outcomes, were obtained. RESULTS: Seven patients with ATTRwt underwent HTx between 2007 and 2015. All patients were male with a mean age of 66 ± 9. Patients had a reduced ejection fraction (mean, 37 ± 14%) and elevated filling pressures pre-HTx (mean pulmonary capillary wedge pressure 22 ± 7 mm Hg) before HTx. Three-year survival was 100%; 1 patient died of pancreatic cancer 45 months post-HTx (1 death per 30.8 patient-years). Oxygen consumption (Δ +6.8 ± 4.9 mL·kg·min) and 6-minute walk distances (Δ +189 ± 60 m) improved. Symptomatic gastrointestinal involvement (n = 2) and peripheral nerve involvement (n = 4) by ATTRwt developed late. CONCLUSIONS: This is the first report of a series of ATTRwt patients receiving HTx in which excellent outcomes are demonstrated. Although cardiac death is averted, systemic manifestations of ATTRwt may develop posttransplantation.

Renal Allograft Outcome After Simultaneous Heart and Kidney Transplantation.

Chronic kidney disease frequently accompanies end-stage heart failure and may result in consideration of simultaneous heart and kidney transplantation (SHKT). In recent years, there has been a significant increase in SHKT. This single-center cohort consisted of 35 patients who underwent SHKT during 1996 to 2015. The aim of this study was to review factors that may predict better long-term outcome after SKHT. Thirteen patients (37%) had delayed graft function (DGF) after transplant (defined as the need for dialysis during the first 7 days after transplant), which was significantly associated with mechanical circulatory support device therapy and high right ventricular systolic pressure before transplant. Most of the recipients had glomerular filtration rate (GFR) ≥50 ml/min/1.73 m2 at 1 and 3 years after transplant (21 of 26 [81%] and 20 of 21 [95%], respectively). Higher donor age was associated with reduced 1-year GFR (p = 0.017), and higher recipient pretransplant body mass index was associated with reduced 3-year GFR (p = 0.008). There was a significant association between DGF and reduced median GFR at 1 and 3 years after transplant (p <0.005). Patient survival rates at 6 months, 1, and 3 years after transplant were 97%, 91%, and 86% respectively. In conclusions, our data support good outcomes after SHKT. Mechanical circulatory support device therapy and pulmonary hypertension before transplant are associated with DGF, which is a risk factor for poor long-term renal allograft function.

Early Gains in Renal Function Following Implantation of HeartMate II Left Ventricular Assist Devices May Not Persist to One Year.

Renal function improves early after left ventricular assist device (LVAD) implantation but later decline has been observed. We sought to determine the occurrence and evaluate possible causes for this decline. In 62 consecutive patients with HeartMateII LVAD with available calculated glomerular filtration rate (GFR, ml/min/1.73 m) 1 year after implant, GFR was assessed repeatedly and possible predictors for decline from 3 to 12 months were investigated. Post-mortem renal specimens for patients supported with an LVAD were evaluated. GFR 54.5 ± 19.5 at admission increased to 66.4 ± 22.3 preoperatively and to 79.2 ± 30.1 ~1 month after implantation. Subsequently at ~3 months GFR declined to 74.7 ± 25.4, at ~6 months to 68.8 ± 23.1, and ~1 year after implant to 63.9 ± 17.7. Glomerular filtration rate at 1 year was significantly lower (p < 0.0001, p < 0.0001, p = 0.005) than GFR 1, 3, and 6 months after implant. Early rise in GFR after surgery was not associated with late decline. Shorter bypass time (ß = -0.09, p = 0.048) and higher albumin 3 months after LVAD (ß = 14.4, p = 0.025) were significantly associated with less later decline in GFR. Arteriosclerosis was identified in autopsy renal specimens. In conclusion, early gains in renal function after LVAD implant are not sustained in many patients. Patient, device, and operative factors may influence long-term renal function in these patients.

Effect of Pretransplant Continuous-Flow Left Ventricular Assist Devices on Cellular and Antibody-Mediated Rejection and Subsequent Allograft Outcomes.

The aim of this study was to evaluate the impact of continuous-flow left ventricular assist devices (CF-LVAD) on subsequent rejection after heart transplantation (HT) by using cellular rejection score and antibody-mediated rejection score (AMRS) and correlating with subsequent allograft outcomes. We retrospectively analyzed 108 consecutive patients who underwent HT without (n = 67) or with (n = 41) previous CF-LVAD in 2008 to 2014. The 24 months cumulative effect of rejection was calculated by using cellular rejection scores and AMRS, based on the total number of rejections divided by valid biopsy samples. Vasculopathy was assessed both by routine coronary angiogram and intravascular ultrasound. Patients who underwent pretransplant CF-LVAD demonstrated a significant increase in the number of cellular rejection episodes as compared with the nonbridged patients, for 1 and 2 years of follow-up (p = 0.026 and p = 0.016), respectively. There were no differences in AMRS (p >0.05) and allograft outcomes, such as vasculopathy and overall survival (p >0.05) over the period of follow-up. Implantation of a CF-LVAD before HT impacts cellular rejection during the post-transplant period. Despite these findings, CF-LVAD does not translate to differences in allograft outcomes after transplant, such as vasculopathy and overall survival over the period of the study. In conclusion, whether this affects longer term outcomes than studied remains to be determined.

Sex Related Differences in the Risk of Antibody-Mediated Rejection and Subsequent Allograft Vasculopathy Post-Heart Transplantation: A Single-Center Experience.

BACKGROUND: Pregnancies may result in antibodies against HLA, a risk factor for antibody-mediated rejection (AMR) and subsequent cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). The aim of this study was to evaluate sex differences in the incidence of AMR events and subsequent risk of CAV among HTx recipients. METHODS: The study comprised 160 patients (51 [32%] women) who underwent HTx in 2008 to 2014. The cumulative effect of AMR events was calculated by AMR score (sum of myocardial biopsy grading divided by number of biopsies taken during 3 years post-HTx). RESULTS: Females had higher levels of anti-HLA I antibodies pre-HTx compared to males which was associated with a history of pregnancies, total number of children and with a higher AMR score at 6 months post-HTx (P < 0.05). Women demonstrated a significant increase in the total incidence of AMR events (27 vs. 7%, P = 0.001) and in AMR scores at 6, 12, 24 and 36 months post-HTx compared to men (P < 0.05). There were no differences in cellular rejection between the groups. A history of AMR events was associated with a significantly increased risk of severe CAV onset (hazard ratio, 7.0; 95% confidence interval, 1.5-31.5; P = 0.012). CONCLUSIONS: Women are at higher risk for AMR post-HTx which subsequently increases their risk for CAV. Females recipients may benefit from closer surveillance to identify AMR at an earlier stage post-HTx, and targeted immunosuppressive therapy to attenuate the development of CAV.

Circulating Galectin-3 Levels Are Persistently Elevated After Heart Transplantation and Are Associated With Renal Dysfunction.

OBJECTIVES: This study evaluated changes in serum levels of galectin (Gal)-3 before and after heart transplantation (HTx) and assessed the role of pre-HTx Gal-3 as a biomarker for post-HTx outcomes. BACKGROUND: Gal-3 is a novel biomarker that reflects cardiac remodeling and fibrosis. Elevated serum Gal-3 levels are associated with poor prognosis in heart failure patients. Whether Gal-3 levels change following HTx and the significance of post-HTx outcomes are unknown. METHODS: Serum Gal-3 levels were measured in 62 patients at 118 days (Interquartile Range [IQR]: 23 to 798 days) before and 365 days (IQR: 54 to 767 days) post HTx. Cardiac tissue taken during routine post-HTx endomyocardial biopsy was evaluated to assess the correlation between tissue Gal-3 staining and serum Gal-3 levels and with the presence of myocardial hypertrophy and fibrosis. RESULTS: Serum Gal-3 levels remained significantly elevated (>17.8 ng/ml) in 35 patients (56%) post HTx. There was a significant inverse correlation between Gal-3 levels and glomerular filtration rate measured before and after HTx (p > 0.005). There was no association between Gal-3 serum level and Gal-3 staining of myocardial tissue or with the presence of myocyte hypertrophy and interstitial fibrosis post HTx. Elevated pre-HTx Gal-3 levels were associated with reduced post-HTx exercise capacity, but this association was not significant after adjustment for age, body mass index, and glomerular filtration rate. CONCLUSIONS: This is the first study to demonstrate the fact that Gal-3 levels remain elevated in the majority of patients despite HTx and is associated with renal dysfunction. Our findings suggest Gal-3 is a systemic rather than cardiac-specific biomarker.

Association Between Early Cardiac Rehabilitation and Long-term Survival in Cardiac Transplant Recipients.

OBJECTIVE: To determine whether participation in early cardiac rehabilitation (CR) after heart transplant (HTx) affects long-term survival. PATIENTS AND METHODS: A retrospective review was conducted in 201 patients who underwent HTx at Mayo Clinic between June 1, 2000, and July 31, 2013. Patients were excluded with multiorgan transplant, no CR data, and follow-up less than 90 days after HTx. Demographic and exercise data at baseline before HTx were collected. Post-HTx exercise capacity, biopsy, CR data, and medications were collected at 1 through 5 and 10 years. RESULTS: Overall survival at 1, 5, and 10 years was 98%, 88%, and 82%, respectively; 29 patients died. Number of CR sessions attended in the first 90 days after HTx predicted survival in multivariate regression, controlling for baseline post-HTx 6-minute walk test (6MWT) results and rejection episodes (hazard ratio, 0.90; 95% CI, 0.82-0.97; P=.007). Additional univariate predictors of survival included pre-HTx 6MWT results, weight at HTx, and body mass index and systolic blood pressure at CR enrollment. Pre-HTx 6MWT results, body mass index, and post-HTx were associated with improvement in peak oxygen consumption. CONCLUSION: This report demonstrates, for the first time, an association between CR and long-term survival in patients after HTx. Further work should clarify the most beneficial aspects of CR.

Current indications, strategies, and outcomes with cardiac transplantation for cardiac amyloidosis and sarcoidosis.

PURPOSE OF REVIEW: We describe the general strategies for the management of cardiac amyloidosis with particular focus on the use of cardiac transplantation for amyloid cardiomyopathy. Within this article, we highlight recent data regarding the use of combined heart transplant-chemotherapy, use of cardiac transplant in mutant amyloid disease, and underutilization of cardiac transplantation in sarcoidosis. RECENT FINDINGS: Several center experiences have been recently published, describing management strategies in AL amyloid, with focus on timing of chemotherapy as it relates to transplant, and in mutant amyloid in particular. SUMMARY: Outcomes after heart transplantation are typically worse than in patients undergoing heart transplantation for nonamyloid disease. Staged heart transplantation followed by autologous stem cell transplant therapy appears to provide the best long-term outcome for AL amyloid in highly selected patients. Mutant transthyretin amyloidosis is a disorder related to production of abnormal transthyretin protein in the liver. Combined heart/liver transplant has been utilized to treat both the production of the abnormal transthyretin protein and manage the cardiac dysfunction in highly selected patients, with favorable outcomes. Wild-type transthyretin amyloidosis occurs predominantly in older men. Cardiac transplantation can be utilized for highly selected patients. Sarcoidosis with cardiac involvement, unresponsive to immunosuppressive therapy, may be treated successfully with cardiac transplantation.

Role of ventricular assist therapy for patients with heart failure and restrictive physiology: Improving outcomes for a lethal disease.

BACKGROUND: Restrictive cardiomyopathy (RCM) patients have poor prognosis due to progressive heart failure characterized by impaired ventricular filling of either or both ventricles. The goal of this study was to evaluate the outcome of end-stage RCM patients after left ventricular assist device (LVAD) implantation and to determine factors that may be associated with improved survival. METHODS: This investigation is a retrospective study of prospectively collected data that include 28 consecutive patients with end-stage RCM who received continuous-flow LVADs at the Mayo Clinic, Rochester, Minnesota. Outcome was assessed by survival with LVAD support until heart transplantation or all-cause mortality. RESULTS: The mean follow-up time post-LVAD implantation was 448 ± 425 days. The mean hospitalization time was 29 ± 19 days and was complicated mainly by post-operative right ventricular (RV) failure requiring short-term medical support. The short-term in-hospital mortality was 14%. Ten patients underwent heart transplantation with 100% survival post-transplant during the follow-up period. One-year survival for patients with LVADs without transplantation was 64%, and was not significantly different between amyloidosis and non-amyloidosis patients. Larger left ventricle (LV) end-diastolic and end-systolic dimensions were significantly associated with improved survival rates (RR = 0.94 and 0.95, p < 0.05, respectively), and left ventricular end-diastolic diameter (LVEDD) ≤46 mm was associated with increased mortality post-LVAD implantation. CONCLUSIONS: LVAD is a feasible, life-saving therapy for end-stage heart failure related to RCM, especially as a bridge to transplant and in patients with larger LV dimensions.

Cardiac transplantation for radiation-induced cardiomyopathy: the Mayo Clinic experience.

BACKGROUND: High-dose radiotherapy to the mediastinum for the treatment of malignancies causes injury to the intrathoracic organs. Coronary artery disease, valvular dysfunction, cardiomyopathy, and chronic constrictive pericarditis are common cardiovascular sequelae during long-term follow-up. Cardiac transplantation is indicated for the surgical treatment of heart failure due to radiation-induced end-stage cardiac disease. METHODS: A retrospective study of radiation-induced cardiomyopathy requiring cardiac transplantation was undertaken from December 1992 to August 2010. RESULTS: Twelve patients (7 men, 5 women), with a mean age of 47.4 years, underwent orthotopic cardiac transplantation. Redo cardiac operations were performed in 9 patients. Lymphoma was the primary malignancy in all patients. Adjuvant chemotherapy was used in 9 patients, and splenectomy was performed in 7. Restrictive cardiomyopathy (n = 8) was the predominant diagnosis. Restrictive lung disease was present in 10 patients (83%). Postoperative chronic kidney injury developed in 3 patients (25%). Hospital mortality was 8.3%. Survival at 1, 5, and 10 years was 91.7%, 75%, and 46.7%, respectively. The overall mean follow-up was 7.7 years (median, 6.1; range, 1.8 to 16.4 years). Late respiratory failure accounted for 3 deaths. CONCLUSIONS: Cardiac transplantation provides satisfactory medium-term to long-term outcome in patients with radiation-induced cardiomyopathy. Secondary malignancies, kidney injury, and respiratory failure contribute to significant postoperative morbidity and death.

Early trends in N-terminal pro-brain natriuretic peptide values after left ventricular assist device implantation for chronic heart failure.

Left ventricular assist devices (LVADs) acutely decrease left ventricular wall stress. Thus, early postoperative levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) should decrease. This study investigated postoperative changes in NT-proBNP levels, the parameters related to changes, and the possible association with complications by performing a retrospective analysis of changes in daily NT-proBNP (pg/ml) levels from admission to discharge both before and after LVAD implantation in a tertiary referral center. For 72 patients implanted with HeartMate II LVADs, baseline NT-proBNP levels were elevated at 3,943 ng/ml (interquartile range 1,956 to 12,964). Preoperative stabilization led to marked decreases in NT-proBNP. Levels peaked 3 days after surgery and subsequently decreased. Patients with complicated postoperative courses had higher early postoperative elevations. By discharge, NT-proBNP decreased markedly but was still 2.83 (1.60 to 5.76) times the age-based upper limit of normal. The 26% reduction in NT-proBNP between admission and discharge was due mostly to the preoperative reductions and not those induced by the LVAD itself. The decrease was not associated with decreases in LV volume. In conclusion, preoperative treatment reduces NT-proBNP values. The magnitude of early postoperative changes is related to the clinical course. Levels at discharge remain markedly elevated and similar to values after preoperative stabilization despite presumptive acute LV unloading.

Cardiac and multiorgan transplantation for end-stage congenital heart disease.

OBJECTIVE: To report our single-center experience with patients who had cardiac and multiorgan transplantation for end-stage congenital heart disease (CHD). PATIENTS AND METHODS: We reviewed records for all patients with CHD who had undergone heart transplantation at Mayo Clinic, Rochester, Minnesota, from November 1, 1990, through June 30, 2012. Patients with cardiomyopathy were excluded, unless CHD was present. RESULTS: Overall, 45 patients had cardiac transplantation for end-stage CHD (mean age, 26.1±18.4 years; range, 1 month to 65 years). Two patients (4%) had combined heart/liver transplantation; 1 (2%) had heart/kidney transplantation. Six patients (13%) had no previous cardiac operation; the remaining 39 patients had a mean of 3 (range, 1-8) previous cardiac operations. Patient survival (95% CI) at 1, 5, and 10 years was 89% (80%-98%), 89% (80%-98%), and 72% (56%-87%), respectively, while graft survival at 1, 5, and 10 years was 89% (80%-98%), 89% (80%-98%), and 61% (44%-78%), respectively. During the same era, the International Society for Heart & Lung Transplantation reported that survival in patients undergoing transplant for non-congenital diagnoses was 85%, 72%, and 56%, respectively. Over a mean follow-up of 8.7±6.2 years, rejection requiring treatment was documented in 35 patients (78%). Eleven patients (24%) have been diagnosed with neoplasia (8 skin, 1 blood, 1 lymph, and 1 other), and 3 patients (7%) have required retransplantation. Four patients (9%) have developed significant coronary vasculopathy; 1 successfully underwent retransplantation, and 3 died 6, 8, and 14 years after transplantation. CONCLUSION: With appropriate patient selection and posttransplant monitoring, survival has improved for patients with complex end-stage CHD. Multiorgan transplantation is an option for selected patients with CHD.

Left ventricular device implantation for advanced cardiac amyloidosis.

The purpose of this study was to analyze the post-hospital outcomes in patients with senile or familial cardiac amyloidosis treated with left ventricular assist device (LVAD) implantation. From December 1, 2008 to May 31, 2012, a total of 9 patients underwent LVAD placement for heart failure secondary to amyloidosis. Prior to LVAD placement, all patients were New York Heart Association (NYHA) Class IV and had a significantly decreased cardiac index (mean 1.93 liters/min/m(2) [1.64 to 2.36]). All patients tolerated LVAD implantation well. Post-operatively, 2 patients died prior to hospital discharge. Three patients died since discharge with a median survival of 13.7 months. Four patients remained alive with a follow-up of 16-24 months. The most common adverse event since placement has been gastrointestinal bleeding (3 of 9 patients). Firm conclusions cannot be drawn from our investigation, but the present observations suggest LVAD implantation is technically feasible for patients with severe heart failure due to advanced cardiac amyloidosis.

Decreased postoperative atrial fibrillation following cardiac transplantation: the significance of autonomic denervation.

BACKGROUND: Endocardial ablation approaches targeting the retroatrial cardiac ganglia to treat atrial fibrillation (AF) have been proposed. However, the potential value using this approach is unknown. Disruption of the autonomic inputs with orthotropic heart transplant (OHT) provides a unique opportunity to study the effects of autonomic innervation on AF genesis and maintenance. We hypothesized that due to denervation, the risk of postoperative AF would be lower following OHT compared to surgical maze even though both groups get isolation of the pulmonary veins. METHODS AND RESULTS: We reviewed 155 OHTs (mean age 52 ± 11 years, 72% males) and used 1:1 age-, sex-, and date-of-surgery-matched two control groups from patients undergoing surgical maze or only coronary artery bypass grafting (CABG). Using conditional logistic regression we compared the odds of AF within 2 weeks following OHT versus controls. Postoperative AF occurred in 10/155 (6.5%) OHT patients. The conditional odds of postoperative AF were lower for OHT as compared to controls (vs maze: odds ratio [OR] 0.27 [95% confidence interval (CI) 0.13-0.57], vs CABG: OR 0.38 [0.17-0.81], P = 0.003; and on additional adjustment for left atrial enlargement, vs maze: OR 0.28 [0.13-0.60], vs CABG: OR 0.14 [0.04-0.47], P = 0.0009). CONCLUSIONS: Risk of postoperative AF is significantly lower with OHT as in comparison to surgical maze. As both surgeries entail isolation of the pulmonary veins but only OHT causes disruption of autonomic innervation, this observation supports a mechanistic role of autonomic nervous system in AF. The benefit of targeting the cardiac autonomic system to treat AF needs further investigation.