Research Spotlight

Mikhalkova, D., E. Novak and A. Cedars (2016). “Short-term costs and hospitalization rates in patients with adult congenital heart disease after pulmonic valve replacement.” Am J Cardiol 118(10): 1552-1557.

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In the adult congenital heart disease (ACHD) population, pulmonary valve replacement (PVR) is a common intervention, its benefit, however, has been incompletely investigated. This study investigates short- and intermediate-term outcomes after PVR in ACHD. Using State Inpatient Databases from the Healthcare Cost and Utilization Project, we investigated both hospitalization rate and financial burden accrued over the 12-month period after PVR compared with the 12 months before. Among 202 patients who underwent PVR, per patient-year hospitalization rates doubled in the year after PVR compared with the year before (0.16 vs 0.36, p = 0.006). With the exception of postprocedural complications, the most common reasons for hospitalization were unchanged after surgery: 22% of patients were admitted with equal or greater frequency after PVR. These patients experienced higher inpatient costs both at index admission and in the year after PVR (p = 0.004 and p <0.001, respectively). Univariate predictors of increased hospitalizations after PVR were age >/=50 years (p = 0.016), transposition of the great arteries, or conotruncal abnormalities (p <0.001), lipid disorders (p = 0.025), hypertension (p = 0.033), and number of chronic conditions >/=4 (p = 0.004). Multivariate analysis identified transposition of the great arteries or conotruncal abnormalities as an independent risk factor for increased hospitalization and cost post-PVR (p /=0.001). In conclusion, short-term costs and hospitalization rates increase after PVR in a small group of patients with ACHD.

Oh, J., M. Barve, C. M. Matthews, E. C. Koon, T. P. Heffernan, B. Fine, E. Grosen, M. K. Bergman, E. L. Fleming, L. R. DeMars, L. West, D. L. Spitz, H. Goodman, K. C. Hancock, G. Wallraven, P. Kumar, E. Bognar, L. Manning, B. O. Pappen, N. Adams, N. Senzer and J. Nemunaitis (2016). “Phase ii study of vigil(r) DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer.” Gynecol Oncol 143(3): 504-510.

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OBJECTIVES: The majority of women with Stage III/IV ovarian cancer who achieve clinical complete response with frontline standard of care will relapse within 2years. Vigil immunotherapy, a GMCSF/bi-shRNA furin DNA engineered autologous tumor cell (EATC) product, demonstrated safety and induction of circulating activated T-cells against autologous tumor in Phase I trial Senzer et al. (2012, 2013) . Our objectives for this study include evaluation of safety, immune response and recurrence free survival (RFS). METHODS: This is a Phase II crossover trial of Vigil (1.0×107 cells/intradermal injection/month for 4 to 12 doses) in Stage III/IV ovarian cancer patients achieving cCR (normal imaging, CA-125/=Grade 3 toxicity related to product was observed. A marked induction of circulating activated T-cell population was observed against individual, pre-processed autologous tumor in the Vigil arm as compared to pre-Vigil baseline using IFNgamma ELISPOT response (30/31 negative ELISPOT pre Vigil to 31/31 positive ELISPOT post Vigil, median 134 spots). Moreover, in correlation with ELISPOT response, RFS from time of procurement was improved (mean 826days/median 604days in the Vigil arm from mean 481days/median 377days in the control arm, p=0.033). CONCLUSION: In conjunction with the demonstrated safety, the high rate of induction of T-cell activation and correlation with improvement in RFS justify further Phase II/III assessment of Vigil.

Roberts, W. C., V. S. Won, A. Vasudevan and J. M. Guileyardo (2016). “Causes of death and heart weights in adults at necropsy in a tertiary texas hospital, 2013-2015.” Am J Cardiol 118(11): 1758-1768.

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The causes of death and heart weights at death appear to be quite different in the USA today than in the first few decades of the last century. We determined the causes of death and heart weights at necropsy in 231 adults and compared the heart weights to those reported in several studies in the first half of the 20th century. Of the 231 patients, 91 (39%) died of a cardiovascular (CV) condition, and 140 (61%), of a non-CV condition. Of the 91 fatal CV disease cases, 48 had fatal coronary artery disease (CAD); of the remaining 183 cases without fatal CAD, 25 had narrowing >75% of 1 or more major epicardial coronary arteries. Thus, 73 of the 231 (32%) patients at necropsy had severe CAD. Comparison between the fatal CV and fatal non-CV cases disclosed variable age (mean 64 years vs mean 57 years) and heart weight (529 g vs 449 g) to be significantly different. Heart weight was found to be the only significantly variable between men and women. Comparison of the heart weights in this study to those recorded as “normal” hearts 75 to 115 years earlier showed that today’s “average” heart is much larger than those reported earlier. In contrast to the earlier studies, heart weight presently appears to increase with age and with an increase in body mass index. In conclusion, early studies in heart weight did not take into account today’s longer survival and therefore a high prevalence of systemic hypertension, diabetes mellitus, obesity (and cardiac adiposity), and the presence of atherosclerotic CAD. Additionally, the cause of death (CV vs non-CV) was rarely considered in the early studies of heart weight.

Sannino, A., R. C. Stoler, B. Lima, M. Szerlip, A. C. Henry, R. Vallabhan, R. C. Kowal, D. L. Brown, M. J. Mack and P. A. Grayburn (2016). “Frequency of and prognostic significance of atrial fibrillation in patients undergoing transcatheter aortic valve implantation.” Am J Cardiol 118(10): 1527-1532.

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The prognostic implications of preexisting atrial fibrillation (AF) and new-onset AF (NOAF) in transcatheter aortic valve implantation (TAVI) remain uncertain. This study assesses the epidemiology of AF in patients treated with TAVI and evaluates their outcomes according to the presence of preexisting AF or NOAF. A retrospective analysis of 708 patients undergoing TAVI from 2 heart hospitals was performed. Patients were divided into 3 study groups: sinus rhythm (n = 423), preexisting AF (n = 219), and NOAF (n = 66). Primary outcomes of interest were all-cause death and stroke both at 30-day and at 1-year follow-up. Preexisting AF was present in 30.9% of our study population, whereas NOAF was observed in 9.3% of patients after TAVI. AF and NOAF patients showed a higher rate of 1-year all-cause mortality compared with patients in sinus rhythm (14.6% vs 6.5% for preexisting AF and 16.3% vs 6.5% for NOAF, p = 0.007). No differences in 30-day mortality were observed between groups. In patients with AF (either preexisting and new-onset), those discharged with single antiplatelet therapy displayed higher mortality rates at 1 year (42.9% vs 11.7%, p = 0.006). Preexisting AF remained an independent predictor of mortality at 1-year follow-up (hazard ratio [HR] 2.34, 95% CI 1.22 to 4.48, p = 0.010). Independent predictors of NOAF were transapical and transaortic approach as well as balloon postdilatation (HR 3.48, 95% CI 1.66 to 7.29, p = 0.001; HR 5.08, 95% CI 2.08 to 12.39, p <0.001; HR 2.76, 95% CI 1.25 to 6.08, p = 0.012, respectively). In conclusion, preexisting AF is common in patients undergoing TAVI and is associated with a twofold increased risk of 1-year mortality. This negative effect is most pronounced in patients discharged with single antiplatelet therapy compared with other antithrombotic regimens.

Yardley, D. A., J. Reeves, E. C. Dees, C. Osborne, D. Paul, F. Ademuyiwa, H. Soliman, T. Guthrie, J. Andersen, L. Krekow, J. Choksi, B. Daniel, M. Danso, A. Favret, S. Oommen, A. Brufsky, J. L. Bromund, Y. Lin, A. B. Ibrahim and P. D. Richards (2016). “Ramucirumab with eribulin versus eribulin in locally recurrent or metastatic breast cancer previously treated with anthracycline and taxane therapy: A multicenter, randomized, phase ii study.” Clin Breast Cancer 16(6): 471-479.

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BACKGROUND: Use of antiangiogenic agents in treatment of metastatic breast cancer (MBC) remains controversial. We evaluated the efficacy and safety of ramucirumab and eribulin versus eribulin alone as third- to fifth-line therapy in women with advanced breast cancer. PATIENTS AND METHODS: In this randomized (1:1), open-label, phase II study, US women aged 18 years or older with 2 to 4 previous chemotherapy regimens for locally recurrent or MBC, previous anthracycline and taxane treatment, and Eastern Cooperative Oncology Group performance status of 0 or 1 received ramucirumab with eribulin or eribulin alone in 21-day cycles (eribulin 1.4 mg/m2 intravenously on days 1 and 8; ramucirumab 10 mg/kg intravenously on day 1). Randomization was stratified according to previous antiangiogenic therapy and triple-negative status. The primary end point was progression-free survival (PFS) in the intention to treat population. RESULTS: One hundred forty-one women were randomized to ramucirumab with eribulin (n = 71) or eribulin alone (n = 70). Median PFS for ramucirumab with eribulin was 4.4 months (95% confidence interval [CI], 3.1-6.7) compared with 4.1 months (95% CI, 3.2-5.6) for eribulin (hazard ratio [HR], 0.83; 95% CI, 0.56-1.23; P = .35). Median overall survival in patients who received ramucirumab with eribulin was 13.5 months (95% CI, 10.4-17.9) compared with 11.5 months (95% CI, 9.0-17.3) in patients who received eribulin alone (HR, 0.91; 95% CI, 0.59-1.41; P = .68); objective response rate was 21% (13 of 62 patients) for the combination and 28% (17 of 60 patients) for eribulin alone. No unexpected toxicity was identified for the combination. CONCLUSION: Ramucirumab combined with eribulin did not significantly improve PFS in advanced MBC.