Citations

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.

Abstract Background Mitral regurgitation (MR) is the most common heart valve disorder worldwide. The contrast between the large burden of MR and the overall low number of performed mitral valve surgery suggest a marked undertreatment of MR patients. Large and comprehensive contemporary data assessing the management and outcome of patients with MR as well as the societal burden of the disease at the Nationwide level are currently lacking. Methods Based on a French mandatory administrative hospital-discharge database, we collected all admissions in France both in public and private hospitals in 2014 and 2015 with MR as primary or secondary code. Patients with infective endocarditis, congenital or rheumatic disease were excluded. Cost were calculated for patients admitted in public hospitals. Results In 2014–2015, 107,412 patients with MR were admitted in France in 1238 public and private hospitals; 74,098 patients (69%) presented with primary MR (PMR) and 33,314 patients (31%) with secondary MR (SMR). Overall 8,676 patients (8%) were operated on (81% PMR) within 1 year and 98,736 (92%) were conservatively managed and constituted our study population. Mean age was 77±15 years (50% were ≥80 years and 12% ≥90 years) and 53% were female. Most of the patients presented with comorbidities and Charlson Index was ≥2 in 53% of the population. In-hospital and one-year mortality were 4.1% and 14.3% respectively. Readmission were very common and one-year mortality/readmission all cause, and one-year mortality / CHF readmission rates were 67% and 34% respectively and increased with age, Charlson Index, CHF at presentation and SMR etiology but events rate remained notably high in the PMR subset (64% and 28% respectively). The total annual cost in public hospitals (initial hospitalisation and readmissions) was 325,716,311 euros. When only readmissions for heart failure were considered (43% of all readmissions), total annual cost was 202,904,869 euros. Conclusion In this large administrative contemporary nationwide database, 1) MR was a common reason for admission and affected an elderly population with frequent comorbidities, 2) less than 10% of patients were offered any intervention, 3) MR was associated with high mortality and readmissions rates in all subsets; 4) MR represented a major societal burden with an extrapolated annual cost between 250 and 400 million euros. These finding highlight the critical need to develop strategies to improve the overall management and outcomes of patients with both primary and secondary MR. Acknowledgement/Funding Edwards Lifesciences

Abstract Background Contemporary and unbiased information regarding the surgical management of patients with mitral regurgitation (MR) at the Nationwide level are scarce. The PMSI, a mandatory administrative database, offers the unique opportunity to assess the presentation and outcomes of all consecutive mitral valve (MV) surgeries performed in France in the contemporary era. Methods We collected all (isolated or combined) MV surgeries performed for MR in France both in public and private hospitals between 2014 and 2016. Based on an algorithm we developed, MR etiology was classified as degenerative (DMR), secondary (SMR) or OTHER (rheumatic, congenital, infective endocarditis or unknown). Results Between January 2014 and December 2016, 18,167 mitral valve surgeries were performed in France (55% repair and 45% replacement; 52% isolated MV surgery). Mean age was 66±12 years and 59% were male. Etiology was DMR in 42%, SMR in 16% and OTHER in 42%. Among DMR, repair rate was 68% overall and 72% in the subset who underwent an isolated MV surgery (70% of all DMR). Repair rates decreased with age, Charlson index and sex (female) (all P<0.0001). Among SMR, a repair was performed in 39% and a combined surgery in 51%. In-hospital mortality and rate of death / readmission for CHF at one year were 3.4% and 13% respectively for DMR (2.4% and 5.5% respectively for isolated DMR) and 7.8% and 17.8% respectively for SMR (5.5% and 12.4% respectively for isolated SMR). Center volume was associated with a lower in-hospital mortality (p=0.002) but not with higher DMR repair rate (P=0.85). Conclusion In this large administrative contemporary nationwide database, 1) DMR surgery was twice as frequent as SMR and more frequently performed isolated; 2) Repair rates in DMR were suboptimal overall but more critically in the elderly and women subsets. 3) Operative mortality and one-year rate of death and readmission were approximately twice as high in SMR than in DMR and overall considerable even for isolated DMR surgery; and 4) In DMR, center volume had no impact on repair rate but an independent impact on outcome. These results underline the need to develop strategies to improve management and outcomes of patients with both degenerative and secondary MR.

Abstract Introduction: The prevalence of venous thrombosis and pulmonary embolism (VTE) increases with age. Definitive VTE diagnosis or exclusion relies on imaging modalities, which are found to be negative in a high proportion of tested patients. Algorithms based on pretest clinical probability (low and intermediate) in conjunction with negative d-dimer test results have reliably excluded VTE sparing the need for additional imaging studies. Currently, the cutoff for a negative d-dimer is based on reference ranges regardless of age of the donor population. Since baseline d-dimer increases with aging, an age-adjusted d-dimer (AADD) cutoff for patients older than 50 years (age*10 ng/mL FEU) has been shown to improve specificity of diagnosis while still maintaining a high sensitivity (>97%) of detecting VTE/PE (Righini, et al. JAMA, 2014). Due to FDA restrictions, clinical laboratories cannot implement and report such AADD cutoffs. Major hurdles include: AADD cutoffs are assay-dependent, and there is a lack of feasible strategy for laboratories to verify the AADD cutoffs. We hypothesize that an adequate study of age-distribution of baseline d-dimer levels of healthy donors can assist the verification of AADD cutoffs and ultimately ensure patient safety in the VTE patient population. Objective: Establish an age dependent reference range for patients 50 years or older with the HemosIL HS 500 D-dimer reagent on the ACL TOP 700 (Instrumentation Laboratory, Bedford MA, USA); and compare this range with the manufacturer provided and literature recommended AADD cutoffs. Methods: D-dimer assay was performed on plasma samples from normal adult donors per the manufacturers' instructions. D-Dimer age, gender distribution and association were analyzed using non-parametric Wilcoxon rank sum, Kolmogorov-Smirnov tests, and quantile regression methods to estimate the 95th percentile to establish a reference range. Results: We studied 241 healthy donors, ranging from 21-91 years of age. Statistically significant differences between males and females (100 [42%] male) were detected (p-value <0.001; p-value =0.0009). Using CLSI guidelines, these statistical differences (median d-dimer for men = 200, while median d-dimer for women = 300) are not considered clinically significant, since only 6% of women would be outside an overall reference range (CLSI guideline states to partition if over 8% for either group would be outside the overall reference range). Using the quantile regression method, a significant association between d-dimer and age was found at the median (P<0.0001). We then established a reference range (95th percentile) for donors younger than age 50 at 635 ng/mL FEU for both men and women and AADD reference range for patients 50 and older (635 + (age - 50)*10 ng/mL) (Figure 1). This reference range was verified with our sample set, with only 6.2% of donors higher than the established reference limit. If we used the non-AADD cutoff provided by the manufacturer for donors younger than 50 (500 ng/mL FEU) and the literature recommended AADD cutoffs for older donors (age*10 ng/mL FEU), 13.3% of our normal donors were above the limits, resulting in not validating this literature reference range per CLSI guidelines in EP28-A3c. These data imply that if both manufacturer and literature recommended AADD cutoffs were adopted, HemosIL HS 500 D-dimer assay should have sufficient sensitivity and negative predictive value, although with slightly lower specificity than those reported by Righini, et al. for detecting VTE/PE. Conclusion: Our study verifies the association between d-dimer level and age and for the first time, to our knowledge, determined AADD normal range for the HemosIL HS 500 D-dimer assay. The manufacturer and literature recommended AADD cutoffs should provide sufficient sensitivity and negative predictive value for VTE/PE exclusion. Figure 1 Age distribution of D-Dimer values (n=241). Figure 1. Age distribution of D-Dimer values (n=241). Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 2859 Background: PTLD is the most common malignancy, other than melanomatous skin cancer complicating solid organ transplantation and has been one of the most commonly observed fatal consequences. The histologies are diverse and include B-cell, T-cell and Hodgkin lymphomas. Rituximab has affected the outcome in CD20+ patients with PTLD. This single institution study sought to identity the outcomes in patients of all histologies and presentations managed in the post-rituximab era. Methods: Patients with solid organ transplantation who were diagnosed with PTLD at Mayo Clinic (Rochester, MN) between December 1970 and October 2009 were identified through the Mayo Clinic Lymphoma Data Base. The rituximab era was defined as patients diagnosed after December 26, 2000, the date of diagnosis for the first patient treated with rituximab in our series. Cox proportional hazards models were used to assess the association of clinical factors and overall survival (OS). Results: 143 patients diagnosed with PTLD between December 1970 and October 2009 were identified. The median age at the time of diagnosis of PTLD was 50 years (range 15–84) with 41 patients (29%) over the age of 60. 93 were male (65%). At a median follow-up of 84 months (range 1–295), 95 patients (65%) have died. The types of organ transplant included renal (39%), liver (31%), cardiac (11%), lung (6%), renal/pancreas (6%), pancreas (4%), and multiorgan (4%). 83% of patients presented with extranodal disease. 28% had involvement of the engrafted organ. 76% of the patients developed PTLD that was EBV+ by in situ hybridization. 62% were stage 3–4. The IPI was intermediate-high in 39% of patients. Initial approaches to management included reduction in immunosuppression (45%), chemotherapy (12%), reduction in immunosuppression with rituximab (12%), rituximab (8%), and radiation therapy (6%). The overall response to therapeutic approaches was 46% in the pre-rituximab era and 56% in the post-rituximab era (chi-squared p=0.25). Patients treated with rituximab had an improved overall survival (HR = 1.66, 95% CI: 0.99–2.79). Patients treated in the rituximab era had improved 1 year survival (76%) compared to patients in the pre-rituximab era (59%) (chi-squared p=0.03). However, the survival advantage in the rituximab era was not maintained in longer follow-up. The median overall survival in the pre-rituximab era was 31 months compared to 56 months in the post-rituximab era (logrank p=0.63). Conclusion: The overall response rates and overall survival are improved with rituximab treatment in CD20+ PTLD, however, the natural history of all PTLD has not improved significantly in the post-rituximab era. New approaches are needed for the prevention and management of all the histologies of PTLD. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Patients with AL and congestive heart failure have a median survival of less than one year. Methods: Between 1994 and 2005, 11 patients underwent sequential heart transplant followed by autologous peripheral blood stem cell transplant (SCT) for treatment of AL. Patients had heart dominant AL with minimal/no other organ impairment and no evidence of multiple myeloma. Results: Patients ranged in age from 35 to 63 years (median 54). All had biopsy proven amyloidosis and monoclonal protein detectable in serum (73%) or urine (100%). Free light chain assay was available prior to SCT in 6 and was abnormal in all. All patients presented with NYHA Class III or IV heart failure. All but two patients had no other organ involved at the time of heart transplant. One patient had his heart transplant at another facility and had renal involvement at the time of heart transplant. One patient had peripheral nerve involvement documented prior to heart transplant. Five patients had progression of amyloid to involve other organs by the time of SCT. These included: renal (6), peripheral nerve (2), macroglossia (3), gastrointestinal (2). The median time from diagnosis to heart transplant was 3 months (range 1 to 5). The median time from heart transplant to SCT was 8 months, (range 3 to 24). Conditioning chemotherapy consisted of melphalan 200 mg /m2 (6 patients) or melphalan 140 mg/m2 (5 patients). Two patients died of complications before day +100, (TRM of 18%). Hematologic remissions were seen in 8 and organ responses in 3. Five were unable to be evaluated for organ response due to the heart transplant. Three died from progressive amyloidosis at 66, 56.7, and 55 months following SCT. The median survival is 56.7 months from SCT. Six are alive with a median follow-up of 24 months, range 9 to 90 months. Among the 6 surviving patients, one patient relapsed and one patient has failed to improve, but 4 patients are in continued remission. One patient developed secondary myelodysplastic syndrome. Conclusions: Heart transplant followed by SCT is feasible and offers durable remissions for carefully selected patients with cardiac AL. Figure Figure

Abstract We present a surgical video highlighting the technical pearls for C7 pedicle screw placement with respect to cervicothoracic constructs. Pedicle screw placement into C7 has been shown to enhance the biomechanical stability of both cervical and cervicothoracic constructs and is safe for patient related outcomes. 1 , 2 Rod placement across the cervicothoracic junction is known to be difficult because of the variable starting point of the C7 pedicle screw, which may cause misalignment of the polyaxial heads with respect to the C7 and C6 screw heads. Using our step-wise method of anatomic screw placement, this potential pitfall is minimized. The T1 pedicle screw is placed first. The C6 lateral mass screw starting point is displaced slightly superiorly from the midpoint of the lateral mass in order to make room for the polyaxial head of the C7 pedicle screw. A small laminotomy is performed in order to find the medial border of the C7 pedicle. Palpation of the medial border allows for an approximation of the pedicle limits. The cranial-caudal angle of drilling is perpendicular to the C7 superior facet, and the medial-lateral trajectory typically falls between 15 and 20 degrees medial. Once the pedicle is cannulated, a ball-tipped probe is used to confirm intraosseous position. A rod is cut and contoured to the appropriate length of the construct. The C7 pedicle screw should capture the rod easily with slight displacement of the polyaxial head. Postinstrumentation anteroposterior and lateral fluoroscopy are performed to confirm good position of the lateral mass and pedicle screws. Patient consent was not required for this cadaveric surgical video.

Background Diastolic pulmonary gradient ( DPG ) was proposed as a better marker of pulmonary vascular remodeling compared with pulmonary vascular resistance ( PVR ) and transpulmonary gradient ( TPG ). The prognostic significance of DPG in patients requiring a left ventricular assist device ( LVAD ) remains unclear. We sought to investigate whether pre‐ LVAD DPG is a predictor of survival or right ventricular ( RV ) failure post‐ LVAD . Methods and Results We retrospectively reviewed 268 patients who underwent right heart catheterization before LVAD implantation from 2007 to 2017 and had pulmonary hypertension because of left heart disease. Patients were dichotomized using DPG ≥7 mm Hg, PVR ≥3 mm Hg, or TPG ≥12 mm Hg. The associations between these parameters and all‐cause mortality or RV failure post LVAD were assessed with Cox proportional hazards regression and Kaplan–Meier analyses. After a mean follow‐up time of 35 months, elevated DPG was associated with increased risk of RV failure (hazard ratio [ HR ]: 3.30; P =0.004, for DPG ≥7 versus DPG <7), whereas elevated PVR ( HR 1.85, P =0.13 for PVR ≥3 versus PVR <3) or TPG ( HR 1.47, P =0.35, for TPG ≥12 versus TPG <12) were not associated with the development of RV failure. Elevated DPG was not associated with mortality risk ( HR 1.16, P =0.54, for DPG ≥7 versus DPG <7), whereas elevated PVR , but not TPG , was associated with higher mortality risk ( HR 1.55; P =0.026, for PVR ≥3 versus PVR <3). Conclusions Among patients with pulmonary hypertension because of left heart disease requiring LVAD support, elevated DPG was associated with RV failure but not survival, while elevated PVR predicted mortality post LVAD implantation.

Significance Statement Because renal function often remains stable in the early stages of autosomal dominant polycystic kidney disease (ADPKD), total kidney volume (TKV) is the most important biomarker of disease severity and progression. The authors developed and validated a fully automated method of simultaneously measuring TKV and total liver volume (TLV) as well as their growth rates from magnetic resonance images. Their findings indicate that the method’s performance is equivalent to the gold standard of manual tracing while requiring a fraction of the time and skill. This approach may address the unmet need for rapid and reliable assessment of TKV and TLV, allowing identification of patients with rapidly progressing ADPKD for emerging drug treatments and serving as a reliable alternative for assessment of disease progression in clinical trials. Background The formation and growth of cysts in kidneys, and often liver, in autosomal dominant polycystic kidney disease (ADPKD) cause progressive increases in total kidney volume (TKV) and liver volume (TLV). Laborious and time-consuming manual tracing of kidneys and liver is the current gold standard. We developed a fully automated segmentation method for TKV and TLV measurement that uses a deep learning network optimized to perform semantic segmentation of kidneys and liver. Methods We used 80% of a set of 440 abdominal magnetic resonance images (T2-weighted HASTE coronal sequences) from patients with ADPKD to train the network and the remaining 20% for validation. Both kidneys and liver were also segmented manually. To evaluate the method’s performance, we used an additional test set of images from 100 patients, 45 of whom were also involved in longitudinal analyses. Results TKV and TLV measured by the automated approach correlated highly with manually traced TKV and TLV (intraclass correlation coefficients, 0.998 and 0.996, respectively), with low bias and high precision (<0.1%±2.7% for TKV and −1.6%±3.1% for TLV); this was comparable with inter-reader variability of manual tracing (<0.1%±3.5% for TKV and −1.5%±4.8% for TLV). For longitudinal analysis, bias and precision were <0.1%±3.2% for TKV and 1.4%±2.9% for TLV growth. Conclusions These findings demonstrate a fully automated segmentation method that measures TKV, TLV, and changes in these parameters as accurately as manual tracing. This technique may facilitate future studies in which automated and reproducible TKV and TLV measurements are needed to assess disease severity, disease progression, and treatment response.