Citations

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.

Background and Purpose: Less is known about the risk factors and outcomes associated with stroke in the current era of increasing heart transplantation (HT) being performed in older patients. The impact of immunosuppression on risk of stroke has not yet been previously studied. We aimed to determine the incidence, risk factors and outcomes of stroke after HT. Methods: We retrospectively analyzed the incidence of ischemic and hemorrhagic strokes and associated outcomes in all consecutive HT recipients transplanted between 1994 and 2016 at a single institution. Results: Of 529 patients who underwent HT, 57 (10.7%) developed stroke, 8.1% had an ischemic events and (2.6%) had a hemorrhagic stroke. Age at HT (adjusted hazard ratio [HR] 1.33; P =0.03) and diabetes (HR, 2.60; P =0.02) were associated with increased risk of ischemic events. Patients with stroke (any type) were more likely to have worse kidney function (HR, 1.81; P =0.02) whereas patients with ischemic events were more likely to undergo combined organ transplantation (HR, 2.01; P =0.05). Cytomegalovirus infection was found to be associated with increased risk of any stroke (HR, 2.09; P =0.02).Conversion from calcineurin inhibitor to sirolimus-based immunosuppression was not found to be associated with a significant change in stroke risk (HR, 1.39; P =0. 45) compared with calcineurin inhibitor maintenance therapy. Stroke of any type and ischemic events were independently associated with increased risk of death (HR, 1.90; P =0.001 and HR, 2.14; P <0.001, respectively). Conclusions: Stroke after HT is associated with increased mortality. Older age at HT, diabetes, renal dysfunction, and CMV infection were associated with greater risk of stroke.

Introduction: Frailty has recently been shown to be associated with increased risk of death after continuous-flow left ventricular assist device (CF-LVAD) implantation as destination therapy (DT), but no data exists specifically analyzing its association with specific early and late adverse events. Methods: Between February 2007 and May 2014, 251 patients (205 male) underwent primary implantation of CF-LVAD at our institution; 157 (63%) were implanted as DT and preoperative frailty assessment was available in 96 pt. Frailty was identified in 58/96 (60%) patients according to the deficit index (31 impairments, disabilities and comorbidities) and defined as > 25% deficits. Age (67 vs. 64 years, p=0.12), male sex (79% vs. 87%, 0.63), chronic kidney disease (64% vs. 63%, p=0.74), creatinine (1.7 vs. 1.5, p=0.1), hemoglobin (11.6 vs. 11.5, p=0.98), and albumin levels (3.7 vs. 3.8, p=0.53) were similar between frail and non-frail pt, while diabetes (59% vs. 13%, p<0.001), ischemic etiology (64% vs. 45%, p=0.04), and preop balloon pump (50% vs. 26%, p=0.01) were significantly different. Results: All patients underwent CF-LVAD implantation and cardiopulmonary bypass time was similar between groups (102 vs. 111 min., p=0.3). There were no significant differences in early adverse events between frail and non-frail pt, including inotrope duration (120 vs. 96 hr., p=0.11), right ventricular failure (19% vs. 13%, p=0.44), respiratory failure (26% vs. 18%, p=0.34), acute renal failure (16% vs. 13%, p=0.69), and hepatic dysfunction (16% vs. 13%, p=0.69). Median length of stay (20 vs. 16 days, p=0.25) and early mortality (12% vs. 8%, p=0.48) were also similar. During a median follow up of 2 years with 224 patient/years of support, any GI bleed (43% vs. 42%, p=0.79), any thromboembolic event (34% vs. 39%, p=0.74), and driveline infection (10% vs. 26%, p=0.052). Conclusions: In this select cohort of patients, frailty did not portend higher risk of adverse events after CF-LVAD implantation for DT despite prior observation that late survival is reduced in these patients. These findings are extremely important in patient selection and counseling of patients prior to LVAD implantation.

Background: Among patients (pts) with coronary artery disease (CAD) who are candidates for coronary artery bypass graft surgery (CABG), a reduced ejection fraction (EF) identifies a high-risk group. The profile of pre-operative, intra-operative and post-operative factors contributing to 30 day (d) mortality in pts with low EF undergoing CABG has not been well characterized. Methods: The STICH trial enrolled 2136 pts with CAD amenable to CABG with an LVEF < 35% who were treated with medical therapy (MED) alone, MED with CABG, or with MED plus CABG and surgical ventricular resconstruction (SVR). Multivariable logistic regression models utilizing extensive baseline, intra-operative and post-operative care variables were developed to determine factors associated with mortality at 30d in a landmark analysis among pts surviving the first 36 hours (h). Results: Among those enrolled, 1460 pts received CABG; 673 (46.1%) on pump, 160 (11.0%) off pump, 132 (9.0%) with a mitral valve procedure (MVR), 393 (26.9%) with SVR, and 102 (7.0%) received CABG with SVR and MVR. Mortality in the operating room (OR) was 0.3 %, within the first 36h was 1.0%, and at 30d was 5.1%. The rate of in-hospital acute myocardial infarction was 0.8%, stroke 1.6%, mediastinitis 1.7%, worsening renal insufficiency 8.4%, and return to OR was 6.9%. Inotropes were used in 43.6% and intra-aortic balloon pump in 18.6%. At 36h, 148 pts (10.2%) remained intubated. Among pts who survived to 36h, a robust multivariable model (Table, c-statistic 0.89) was developed to predict 30d mortality. A prolonged intubation time (>36h) was the strongest marker of 30d mortality (odds ratio 7.4, 95% CI 3.8, 14.5, p<0.0001). Conclusions: Among pts with ischemic heart failure, CABG can be performed with a low rate of complications and intra-operative mortality. Prolonged intubation time (>36h) after CABG is an integrated clincal marker that may serve to identify those pts with the least likelihood of survival to 30d.

Background —Patients who have had previous CABG may subsequently develop significant mitral valve (MV) dysfunction that requires surgical intervention. Methods and Results —We reviewed 80 consecutive patients who had had previous CABG and who underwent MV surgery between January 1972 and March 1997. Forty-seven (59%) had initial CABG elsewhere, and 5 had had previous CABG twice. The mean interval between the previous CABG and the MV surgery was 6.3 years (range, 4.4 months to −17 years). At least 15 patients had grade 1/4 to 2/4 mitral regurgitation at initial CABG. The study group included 59 men and 21 women, with a mean study group age of 65.5 years. Ninety-four percent had symptoms of congestive heart failure, 60% had angina, 96% were in NYHA class III to IV, and 37% had an ejection fraction (EF) <50%. Origin of the MV disease was ischemic in 33 patients, myxomatous in 19, combined ischemic and myxomatous in 16, rheumatic in 5, infective in 3, and unknown in 4. MV repair was performed in 46 patients (58%) and MV replacement (MVR) in 34. Concomitant repeat CABG was performed in 38 (48%) patients. In-hospital mortality was 7 of 80 (8.8%); no early death occurred among patients with myxomatous disease. EF <50% was the only significant predictor of early mortality. Overall 1-, 5-, and 10-year survival was 83.8%, 55.6%, and 34.4% respectively. Predictors of late cardiac death were preoperative NYHA class IV ( P =0.0006), urgent or emergency operation ( P <0.0001), use of intra-aortic balloon pump ( P =0.002), and EF <50% ( P =0.01). Seven patients had an additional reoperation: 4 received CABG, 2 MVR, and 2 MV repair. Conclusions —Ischemic, myxomatous, rheumatic, or infective MV dysfunction may develop subsequently after CABG. MVR or MV repair after previous CABG is associated with an acceptably low operative risk and good relief of symptoms. Left ventricular function is strongly correlated with both hospital and late mortality. Surgery should be done before LV dysfunction develops.

Background —Proliferation of the intima is an early lesion of saphenous vein graft disease. Early patency rates of radial artery grafts are acceptable, but little is known about their risk of intimal hyperplasia. Methods and Results —To develop a model of intimal hyperplasia, we incubated human saphenous veins, internal mammary arteries, and radial arteries (n=6, 8, and 10, respectively) in an organ culture with Rosewell Park Memorial Institute 1640 (30% serum) for 0, 4, 7, 10, and 14 days. Quantitative histological studies were performed, and the average intimal-to-medial (I/M) ratio was calculated for each incubation interval. After 10 and 14 days of culture, the I/M ratio increased in the saphenous veins ( P =0.03, P =0.04 versus 0 day, respectively). No significant increase occurred in the I/M ratio in either the internal mammary or radial arteries. Next, the ability of adenoviral gene transfers to inhibit intimal hyperplasia in the saphenous veins was evaluated. Adenoviral-mediated gene transfer of nitric oxide synthase significantly reduced the I/M ratio at 14 days compared with vehicle ( P =0.001) and virus ( P =0.004) controls. Conclusions —The human saphenous vein has a greater propensity for intimal hyperplasia than arterial grafts; the human radial artery behaves similarly to the internal mammary artery. In the future, gene therapy may augment nitric oxide synthase, limiting vein graft disease.

Background —The role of surgical closure of patent foramen ovale (PFO) for cerebral infarction (CI) or transient ischemic attack (TIA) resulting from paradoxical embolism is unclear, and its effect on recurrence is unknown. Our objective was to determine the outcome of surgical closure of PFO in patients with a prior ischemic neurological event, define the rate of CI or TIA recurrence after PFO closure, and identify risk factors for these recurrences. Methods and Results —We retrospectively analyzed 91 patients (58 men, 33 women) with ≥1 previous cerebrovascular ischemic events who underwent surgical PFO closure between April 1982 and March 1998. The presence of a PFO with a right-to-left shunt was confirmed with transesophageal echocardiography. Mean age was 44.2±12.2 years. The index event was a CI in 59 and a TIA in 32; a Valsalva-like episode preceded the event in 15 patients. Deep venous thrombosis was documented in 9 patients, and a hypercoagulable state was identified in 10. Surgical closure was performed with extracorporeal circulation by either direct suture (n=82) or patch closure (n=9). Limited incisions were used in 18.7% of patients. There was no operative mortality. Morbidity included transient atrial fibrillation (n=11), pericardial drainage for effusion (n=4), exploration for bleeding (n=3), and superficial wound infection (n=1). Follow-up totaled 176.3 patient-years, and mean follow-up was 2.0 years. No one had a CI, and 8 had a TIA during follow-up, with 1 caused by temporal arteritis. Transesophageal echocardiography demonstrated all closures to be intact in these patients. The overall freedom from TIA recurrence during follow-up was 92.5±3.2% at 1 year and 83.4±6.0% at 4 years. Having multiple neurological events before PFO closure was the only significant risk factor for TIA or CI recurrence after closure by univariate analysis ( P =0.05); the small number of post-PFO closure cerebral ischemic events precluded multivariate analysis. Conclusions —Surgical closure of PFO can be performed with minimal morbidity and mortality. PFO closure may decrease the risk of recurrent stroke or TIA and may avoid lifelong anticoagulation in the young adult if there is no other indication. Recurrent cerebrovascular ischemic events after surgery should prompt further evaluation to identify causes other than paradoxical embolism.

Background Pericardiectomy for post-radiation constrictive pericarditis has been reported to generally have unfavorable outcomes. This study sought to evaluate surgical outcomes in a large cohort of patients undergoing pericardiectomy for radiation-associated pericardial constriction. Methods A retrospective analysis of all patients (≥18years) who underwent pericardiectomy for a diagnosis of constrictive pericarditis with a prior history of mediastinal irradiation from June 2002 to June 2019 was conducted. There were 100 patients (mean age 57.2±10.1 years, 49% females) who met the inclusion criteria. Records were reviewed to look at surgical approach, extent of resection, early mortality and late survival. Results The overall operative mortality was 10.1% (n=10). The rate of operative mortality decreased over the study period; however, the test of trend was not statistically significant (P=0.062). Hodgkin’s disease was the most common malignancy (64%) for which mediastinal radiation had been received. Only 27% patients had an isolated pericardiectomy, and concomitant pericardiectomy and valve surgery was performed in 46% patients. Radical resection was performed in 50% patients, whereas 47% patients underwent a subtotal resection. Prolonged ventilation (26%), atrial fibrillation (21%) and pleural effusion (16%) were the most common post-operative complications. The overall 1,5- and 10-years survival was 73.6%, 53.4% and 32.1% respectively. Increasing age (HR 1.044, 95%CI 1.017-1.073) appeared to have a significant negative effect on overall survival in the univariate model. Conclusion Pericardiectomy performed for radiation associated constrictive pericarditis has poor long-term outcomes. The early mortality, though high (~10%), has been showing a decreasing trend in the test of time.