Research Spotlight

Kilic, A., J. N. Katz, S. M. Joseph, M. A. Brisco-Bacik, N. Uriel, B. Lima, R. Agarwal, R. Bharmi, D. J. Farrar and S. Lee (2018). “Changes in pulmonary artery pressure before and after left ventricular assist device implantation in patients utilizing remote haemodynamic monitoring.” ESC Heart Fail Oct 23. [Epub ahead of print].

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AIMS: The time course of changes in pulmonary artery (PA) pressure due to left ventricular assist devices (LVADs) is not well understood. Here, we describe longitudinal haemodynamic trends during the peri-LVAD implantation period in patients previously implanted with a remote monitoring PA pressure sensor. METHODS AND RESULTS: We retrospectively studied PA pressure trends in patients implanted with CardioMEMS PA pressure sensor between October 2007 and March 2017 who subsequently had an LVAD procedure. Data are presented as mean +/- standard deviation, and P-values are calculated using standard t-test with equal variance. Among 436 patients in cohort, 108 (age 58 +/- 11 years, 82% male) received an LVAD and 328 (age 60 +/- 13 years, 70% male) did not. The mean PA pressure at sensor implant was higher by 29% (P < 0.001) among patients who later received LVAD. Mean PA pressure 6 months prior to LVAD implant was 35.5 +/- 8.5 mmHg, increasing to 39.4 +/- 9.9 mmHg (P = 0.04) at 4 weeks before LVAD, and then decreasing 27% to 28.8 +/- 8.4 mmHg (P < 0.001) at 3 months post-implant and stabilizing at 31.0 +/- 9.4 mmHg at 1 year. CONCLUSIONS: Patients who later receive LVADs have higher PA pressures at sensor implant and show a further increase leading up to LVAD implantation. There is a significant reduction of PA pressures post-LVAD implantation that persists long term. PA pressure monitoring may aid in the clinical decision making of timing for LVAD implantation and in management of LVAD patients.

Jester, R., I. Znoyko, M. Garnovskaya, J. N. Rozier, R. Kegl, S. Patel, T. Tran, M. Abedalthagafi, C. M. Horbinski, M. Richardson, D. J. Wolff, R. Lapadat, W. Moore, F. J. Rodriguez, J. Mull and A. Olar (2018). “Expression of renal cell markers and detection of 3p loss links endolymphatic sac tumor to renal cell carcinoma and warrants careful evaluation to avoid diagnostic pitfalls.” Acta Neuropathol Commun Oct 19; 6(1):107.

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Endolymphatic sac tumor (ELST) is a rare neoplasm arising in the temporal petrous region thought to originate from endolymphatic sac epithelium. It may arise sporadically or in association with Von-Hippel-Lindau syndrome (VHL). The ELST prevalence in VHL ranges from 3 to 16% and may be the initial presentation of the disease. Onset is usually in the 3rd to 5th decade with hearing loss and an indolent course. ELSTs present as locally destructive lesions with characteristic computed tomography imaging features. Histologically, they show papillary, cystic or glandular architectures. Immunohistochemically, they express keratin, EMA, and variably S100 and GFAP. Currently it is recommended that, given its rarity, ELST needs to be differentiated from other entities with similar morphologic patterns, particularly other VHL-associated neoplasms such as metastatic clear cell renal cell carcinoma (ccRCC). Nineteen ELST cases were studied. Immunohistochemistry (18/19) and single nucleotide polymorphism microarray testing was performed (12/19). Comparison with the immunophenotype and copy number profile in RCC is discussed. Patients presented with characteristic bone destructive lesions in the petrous temporal bones. Pathology of tumors showed characteristic ELST morphology with immunoexpression of CK7, GFAP, S100, PAX-8, PAX-2, CA-9 in the tumor cells. Immunostaines for RCC, CD10, CK20, chromogranin A, synaptophysin, TTF-1, thyroglobulin, and transthyretin were negative in the tumor cells. Molecular testing showed loss of 3p and 9q in 66% (8/12) and 58% (7/12) cases, respectively. Immunoreactivity for renal markers in ELST is an important diagnostic caveat and has not been previously reported. In fact, renal markers are currently recommended in order to rule out metastatic RCC although PAX gene complex and CA-9 have been implicated in the development of the inner ear. Importantly copy number assessment of ELST has not been previously reported. Loss of 3p (including the VHL locus) in ELST suggests similar mechanistic origins as ccRCC.

Jarvholm, S., A. M. Warren, M. Jalmbrant, N. Kvarnstrom, G. Testa and L. Johannesson (2018). “Preoperative psychological evaluation of uterus transplant recipients, partners, and living donors: Suggested framework.” Am J Transplant 18(11): 2641-2646.

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Uterus transplant has become a real option for women with uterine-factor infertility to become pregnant and give birth. The screening before uterus transplant consists of a multidisciplinary evaluation and includes the potential recipient, living donor, and, to some extent, the recipient’s partner and future co-parent. The psychological evaluation has evolved from broad-based screening in the first uterus transplant trial, where the aim was to find suitable candidates for a novel experimental procedure with an unknown outcome, to a more directed screening with specific psychological domains for a complex infertility treatment with promising results. This report outlines a consensus by investigators with pioneering experience in the field of the key factors and suggests a framework for psychological evaluation of recipients and their partners as well as for live uterus donors before uterus transplant. We identify the main areas of particular value to the recipient screening (general psychological health, factors associated with infertility, and medication adherence), the partner (general psychological health and factors associated with infertility), and the living donor (psychological health and motivation to donate, especially in the case of the nondirected donor).

Idriss, R., J. Hasse, T. Wu, F. Khan, G. Saracino, G. McKenna, T. Giuliano, J. Trotter, G. Klintmalm and S. K. Asrani (2018). “Impact of prior bariatric surgery on perioperative liver transplant outcomes.” Liver Transpl Oct 28. [Epub ahead of print].

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Bariatric surgery (BS) is effective in treating morbid obesity but the impact of prior BS on candidacy for liver transplantation (LT) is unclear. We examined 78 cirrhotic patients with prior BS compared with a concurrent cohort of 156 patients matched by age, MELD score, and underlying liver disease. We compared rates of transplant denial after evaluation, delisting on the waitlist (WL) and survival after LT. The median time from BS to LT evaluation was 7 years. Roux-en-Y gastric bypass was the most common BS procedure performed (63% of cohort). Nonalcoholic fatty liver disease was the leading etiology for liver cirrhosis (47%). Delisting/death on WL was higher among patients with BS (33.3% vs 10.1% P = 0.002) and transplantation rate was lower (48.9% vs 65.2% P =0.03). Intent-to-treat survival from listing to 1 year after LT was lower in the BS vs. concurrent cohort (1-year survival 84% vs 90%, p=0.05). On adjusted analysis, history of BS was associated with an increased risk of death on the WL (HR 5.7, 95% CI 2.2-15.1) but this impact was attenuated (HR, 4.9, 95% CI 1.8-13.4) by presence of malnutrition. When limited to matched controls by gender, mortality attributed to BS was no longer significant for women (p=0.37) but was significant for males (p=0.046). Sarcopenia, as captured by skeletal muscle index, was calculated in a subset of patients (n=49). The total skeletal surface area was lower in the BS group (127cm(2) (105-141) vs 153cm(2) (131-191) p = 0.005). Rates of sarcopenia were higher among patients delisted after listing (71.4% vs. 16.7%, p=0.04). Conclusion History of BS was associated with higher rates of delisting on the WL as well as lower survival from time of listing on intent-to-treat analysis. Presence of malnutrition and sarcopenia among patients with BS may contribute to worse outcomes.

Hebeler, K. R., H. Baumgarten, J. J. Squiers, J. Wooley, B. D. Pollock, C. Mahoney, G. Filardo, B. Lima and J. M. DiMaio (2018). “Albumin Is Predictive of 1-Year Mortality After Transcatheter Aortic Valve Replacement.” Ann Thorac Surg 106(5): 1302-1307.

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BACKGROUND: A validated model for predicting 1-year outcomes after transcatheter aortic valve replacement (TAVR) does not exist. TAVR-specific risk models may benefit from frailty markers, and sarcopenia may represent an objective frailty marker. This study assessed the predictive ability of sarcopenia and frailty markers on 1-year mortality after TAVR. METHODS: We evaluated 470 patients undergoing TAVR at a single center. Frailty was assessed using four markers: gait speed, hand grip strength, serum albumin, and Katz activities of daily living. Sarcopenia was measured as the cross-sectional psoas muscle area on pre-TAVR computed tomography. Performance of four models incorporating The Society of Thoracic Surgeons Predicted Risk of Mortality, frailty, or sarcopenia metrics, or both, for predicting 1-year mortality was assessed with area under the curve, Hosmer-Lemeshow statistics, and calibration plots. RESULTS: A total of 63 deaths (13.4%) deaths occurred by 1 year. The Society of Thoracic Surgeons Predicted Risk of Mortality alone was poorly predictive of 1-year mortality (area under the curve, 0.52; 95% confidence interval, 0.42 to 0.68). Only the model including sarcopenia and all frailty markers (area under the curve, 0.61; 95% confidence interval, 0.53 to 0.68) significantly improved predictive ability compared with The Society of Thoracic Surgeons Predicted Risk of Mortality alone (p = 0.05). Albumin was the only frailty marker significantly associated with increased risk for 1-year mortality (p = 0.03). Psoas muscle area, as a surrogate for sarcopenia, was not significantly associated with increased risk for 1-year mortality. CONCLUSIONS: Most of the commonly used pre-TAVR risk assessments are poorly predictive of 1-year mortality. Albumin was the only frailty marker that was associated with higher mortality. Future studies should investigate whether optimization of nutritional status can improve outcomes after TAVR.