R.K. Cheng

CSU Mentor, Long Beach, California, United States

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Publications (37)201.05 Total impact

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    ABSTRACT: Studies on outcomes among patients with heart failure (HF) with preserved left ventricular ejection fraction (HFpEF), borderline left ventricular ejection fraction (HFbEF), and reduced left ventricular ejection fraction (HFrEF) remain limited. We sought to characterize mortality and readmission in patients with HF in the contemporary era. Get With The Guidelines-HF was linked to Medicare data for longitudinal follow-up. Patients were grouped into HFpEF (left ventricular ejection fraction [EF] ≥50%), HFbEF (40% ≤ EF < 50%), and HFrEF (EF <40%). Multivariable models were constructed to examine the relationship between EF and outcomes at 30 days and 1 year and to study trends over time. A total of 40,239 patients from 220 hospitals between 2005 and 2011 were included in the study: 18,897 (47%) had HFpEF, 5,626 (14%) had HFbEF, and 15,716 (39%) had HFrEF. In crude survival analysis, patients with HFrEF had slightly increased mortality compared with HFbEF and HFpEF. After risk adjustment, mortality at 1 year was not significantly different for HFrEF, HFbEF, and HFpEF (HFrEF vs HFpEF, hazard ratio [HR] 1.040 [95% CI 0.998-1.084], and HFbEF vs HFpEF, HR 0.967 [95% CI 0.917-1.020]). Patients with HFpEF had increased risk of all-cause readmission compared with HFrEF. Conversely, risk of cardiovascular and HF readmissions were higher in HFrEF and HFbEF compared with HFpEF. Among patients hospitalized with HF, patients with HFpEF and HFbEF had slightly lower mortality and higher all-cause readmission risk than patients with HFrEF, although the mortality differences did not persist after risk adjustment. Irrespective of EF, these patients experience substantial mortality and readmission highlighting the need for new therapeutic strategies. Copyright © 2014 Elsevier Inc. All rights reserved.
    American Heart Journal 11/2014; 168(5):721-730.e3. DOI:10.1016/j.ahj.2014.07.008 · 4.56 Impact Factor
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    ABSTRACT: Background: The use of left ventricular assist devices has grown rapidly in recent years for patients with end-stage heart failure. A significant proportion of patients require both left- and right-sided support with biventricular assist devices (BiVADs) as a bridge to transplantation. Traditionally, these patients have waited in the hospital until they receive a transplant. Purpose: The aim of this study was to characterize the clinical course of BiVAD patients discharged to home to await heart transplantation. Methods: Between November 2009 and July 2011, 24 adult patients underwent Thoratec paracorporeal BiVAD placement at the University of California Los Angeles, all with an Interagency Registry for Mechanically Assisted Circulatory Support score 1 or 2. The disposition, complications, and rehospitalizations of these subjects were retrospectively reviewed. Results: Fourteen of the 24 patients were successfully discharged to home, with a mean time of 60 +/- 27 days from BiVAD implantation to discharge. Ninety-three percent (13/14) of the patients sent home went on to be transplanted. Eleven of the 14 (79%) came in from home to receive their transplant. The mean time from BiVAD implantation to transplantation was 100 +/- 65 days. Of the 14 patients discharged to home, there were 18 readmissions in 8 patients. Conclusion: In this small single-center review, we found that complex medical patients with BiVADs can be discharged to home and can await a heart transplant from home under the close management of multidisciplinary acute care and outpatient teams.
    The Journal of cardiovascular nursing 06/2014; DOI:10.1097/JCN.0000000000000168 · 1.81 Impact Factor
  • Richard K Cheng, Jamil Aboulhosn, Ali Nsair
    JACC Cardiovascular Interventions 05/2014; 7(6). DOI:10.1016/j.jcin.2013.09.015 · 7.44 Impact Factor
  • The Journal of Heart and Lung Transplantation 04/2014; 33(4):S66. DOI:10.1016/j.healun.2014.01.211 · 5.61 Impact Factor
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    ABSTRACT: Cyclin A2 (Ccna2), normally silenced after birth in the mammalian heart, can induce cardiac repair in small-animal models of myocardial infarction. We report that delivery of the Ccna2 gene to infarcted porcine hearts invokes a regenerative response. We used a catheter-based approach to occlude the left anterior descending artery in swine, which resulted in substantial myocardial infarction. A week later, we performed left lateral thoracotomy and injected adenovirus carrying complementary DNA encoding CCNA2 or null adenovirus into peri-infarct myocardium. Six weeks after treatment, we assessed cardiac contractile function using multimodality imaging including magnetic resonance imaging, which demonstrated ~18% increase in ejection fraction of Ccna2-treated pigs and ~4% decrease in control pigs. Histologic studies demonstrate in vivo evidence of increased cardiomyocyte mitoses, increased cardiomyocyte number, and decreased fibrosis in the experimental pigs. Using time-lapse microscopic imaging of cultured adult porcine cardiomyocytes, we also show that Ccna2 elicits cytokinesis of adult porcine cardiomyocytes with preservation of sarcomeric structure. These data provide a compelling framework for the design and development of cardiac regenerative therapies based on cardiomyocyte cell cycle regulation.
    Science translational medicine 02/2014; 6(224):224ra27. DOI:10.1126/scitranslmed.3007668 · 14.41 Impact Factor
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    ABSTRACT: Our insights into different system levels of mechanisms by left ventricular assist device support are increasing and suggest a complex regulatory system of overlapping biological processes. To develop novel decision-making strategies and patient selection criteria, heart failure and reverse cardiac remodeling should be conceptualized and explored by a multifaceted research strategy of transcriptomics, metabolomics, proteomics, molecular biology, and bioinformatics. Knowledge of the molecular mechanisms of reverse cardiac remodeling is in its early stages, and comprehensive reconstruction of the underlying networks is necessary.
    Heart Failure Clinics 01/2014; 10(1 Suppl):S57-62. DOI:10.1016/j.hfc.2013.08.007 · 1.41 Impact Factor
  • Heart Failure Clinics 01/2014; 10(1):S57–S62. · 1.41 Impact Factor
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    ABSTRACT: Heart failure (HF) and obesity are commonly seen in the USA. Although obesity is associated with traditional cardiovascular disease, its relationship with HF is complex. Obesity is an accepted risk factor for incident HF. However, in patients with established HF, there exists a paradoxical correlation, with escalating BMI incrementally protective against adverse outcomes. Despite this relationship, patients with HF may desire to lose weight to reduce comorbidities or to improve quality of life. Thus far, studies have shown that intentional weight loss in obese patients with HF does not increase risk, with strategies including dietary modification, physical activity, pharmacotherapy, and/or surgical intervention.
    Expert Review of Cardiovascular Therapy 08/2013; DOI:10.1586/14779072.2013.824691
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    ABSTRACT: Purpose ARVC outcomes post-HT pts have not been well studied. Criteria were established in 1994 & revised in 2010. We sought to better characterize ARVC pts in a national cohort. Methods and Materials 30605 HT-only pts were identified from UNOS (1994-2011). Exclusions (24%):<18y, re-HT & follow up loss. Non-ARVC: ischemic, restrictive, dilated, hypertrophic & other. Survival was censored at 12y. Multivariate Cox proportional hazard regression analysis was adjusted for age, sex, DM, race, ischemic time, HD, life support, wait time & HLA mismatch. Results There were 65 ARVC & 30540 non-ARVC pts (2% restrictive, 2% hypertrophic, 44% dilated, 47% ischemic, 7% other). ARVC pts were younger (p=0.0002) with less VAD use (p=0.001), decreased pulmonary artery pressures (p=0.0001), & associated with higher PRA (p<0.001)(Table). Survival (1, 5 & 10y) was: ARVC (87, 80, 80%) & non-ARVC (87, 72, 53%) (Figure). Unadjusted HR for all-cause mortality was 0.57 (0.31-1.06). After adjustment: 0.77 (0.40-1.48, p=NS). ARVC survival was similar to hypertrophic, dilated & other while significantly better than restrictive & ischemic (1B). Conclusions This is the largest reported series of ARVC post-HT survival. Survival was similar to non-ARVC pts, with improved survival over ischemic & restrictives. ARVC was associated with less VAD use & lower filling pressures, suggestive of predominant right ventricular dysfunction.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S23. DOI:10.1016/j.healun.2013.01.040 · 5.61 Impact Factor
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    ABSTRACT: Pre-HT diagnosis of ICM has become less prevalent over time in large part due to advances in revascularization leading to more advanced presentations at time of HT. We sought to study survival by era in this population.Methods and Materials39759 HT recipients (exclusions included age<18 & multiorgan) were identified from UNOS (1987-2011) & stratified by etiology & era. Survival was censored at 12y. Multivariate Cox proportional hazard regression analysis was adjusted for age, sex, DM, race, ischemic time, dialysis, life support, wait time & HLA mismatch.Results19087 (48%) pts were ischemic (Era 1-1987-94: 6107 (52%); Era 2-1995-99: 4703 (52%); Era 3-2000-2004: 3696 (47%); Era 4-2005-11: 4581 (41%). Age and diabetes increased by era (p < 0.001). Prior cardiac surgery increased by era (Era 1-4: 0.1%, 0.5%, 10.0%, 55%; p < 0.001). VAD use increased by era (Era 1-4: 3%, 13%, 24%, 30%; p < 0.001). Creatinine progressively decreased by era (p<0.001). Pts listed Status 1 increased by era (Era 1-4: 53%, 69%, 72%, 87%; p <0.001). Survival is shown in Figure 1 by ICM (A); era & ICM (B-D). Unadjusted HR (CI) for all-cause mortality (as compared to era 1) was era 2 [0.84 (0.80-0.89)]; era 3 [0.75 (0.71-0.79)] & era 4 [0.67 (0.62-0.72)]. After adjustment, all-cause mortality (as compared to era 1) was era 2 [0.71 (0.67-0.76)]; era 3 [0.61 (0.56-0.65)] & era 4 [0.53 (0.48-0.58)].Conclusions Post HT survival improves by era in ICM pts despite increasing pt complexity (i.e. increased Status 1 pts, prior cardiac surgery, older age, diabetes, and increased VAD use).
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S112. DOI:10.1016/j.healun.2013.01.233 · 5.61 Impact Factor
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    ABSTRACT: CKD is common in pts awaiting HT & may be associated with worse outcomes post-HT. CKD stage threshold where H+K is beneficial compared to HT-only is not well defined.Methods and Materials30424 HT-only & 563 H+K pts were identified from UNOS(1987-2011) & stratified by CKD stage using the MDRD formula. Exclusions(41%):<18y), re-HT & follow-up (FU) loss. Survival was censored at 12y & multivariate Cox proportional hazard regression models were adjusted for age, sex, DM, race, ischemic time, dialysis, etiology, life support, wait time & HLA mismatch.ResultsCKD 2 (39%) & 3(36%) were most prevalent compared to CKD 1(19%), 4(3%) & 5(3%) in HT-only pts. Amongst H+K pts, CKD 3 (20%), 4(18%) & 5(56%) were most prevalent. FU began at time of HT (mean 65 ± 57 months). 12688 pts died (41% HT & 31% HK, p<0.001). Crude survival is shown (Figure). Unadjusted HR for all-cause mortality (compared to CKD 3 HT) in H+K showed:CKD 3[0.68 (0.44-1.03)]; CKD 4[1.11 (0.78-1.57)]; CKD 5[1.05 (0.86-1.26)]. After adjustment: CKD 3[0.66 (0.42-1.04)]; CKD 4[1.07 (0.75-1.53)]; CKD 5(0.94 (0.73-1.21)]. Comparing HT vs H+K in each stage individually: CKD 3[1.67 (1.10-2.54)] vs [0.60 (0.39-0.91)]; CKD 4[1.50 (1.05-2.15)] vs [0.66 (0.46-0.95)]; CKD 5[1.83 (1.48-2.27)] vs [0.54 (0.44-0.67)].ConclusionsHT-only survival is significantly diminished in CKD 3-5 compared to CKD 1-2. However, H+K appears protective for CKD stages 3-5, with similar mortality compared to HT-only with normal renal function In each individual stage 3, 4, & 5, HT-only has increased mortality compared to H+K. These results suggest CKD stages 3-5 should undergo H+K rather than HT-only. Prospective study is warranted to verify these results.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S144. DOI:10.1016/j.healun.2013.01.325 · 5.61 Impact Factor
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    ABSTRACT: We sought to characterize the ACHD HT experience at a single referral institute.Methods and MaterialsWe analyzed our HT database. All OHT patients aged ≥ 18 years from 2001-2011 were included. Longitudinal survival was examined with Kaplan-Meier & adjusted Cox PH regression. Follow-up time was censored at 1 year. Data from UNOS registry (2001-2011) was compared.ResultsIn our institution, 728 HT patients were identified, with 699 non-ACHD & 29 ACHD. Overall, 34.6% were ischemic & 65.4% were non-ischemic. Overall age was 52.4 ± 13.8 years, with ACHD younger than non-ACHD (34.9 ± 14.6 versus 53.1 ± 13.3, p < 0.001). Survival at 30-, 60-, & 365 days was 93.1%, 89.7%, 86.2% in ACHD, & 98.4%, 97.9%, 91.2% in non-ACHD, respectively (Figure 1a). After adjusting for age, ACHD had worse survival at 30 days [OR 5.3 (95% CI 1.0-28.7), p = 0.05], 60 days [5.7 (1.4-22.7), 0.015], & 6 months [3.9 (1.3-12.1), 0.017]. This difference resolved at 1 year [1.8 (0.6-5.3), 0.277]. In UNOS, there were 465 ACHD HT-only from 2001-2011. When comparing our experience to UNOS (Figure 1b), there was no significant difference, but an apparent trend toward improved survival in our ACHD cohort (30-, 60- & 365-day survival of 84.2%, 81.9%, & 77.4%).Conclusions Management of ACHD patients with heart failure remains challenging with OHT as a viable strategy for end-stage disease. In our experience, ACHD patients have increased mortality early post-transplant that persists to 6 months. However, ACHD patients have similar survival by 1 year. When compared to UNOS ACHD, there was no significant difference in survival for 2001-2011, although a trend toward improved survival existed despite a complex referral base.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S206. DOI:10.1016/j.healun.2013.01.511 · 5.61 Impact Factor
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    ABSTRACT: MOD is a major cause of mortality after MCSD implantation in heart failure patients. We hypothesized that WGCNA can model the MOD inflammatory response.Methods and MaterialsWe analyzed peripheral blood mononuclear cell gene expression of 29 MCSD patients between 3/2010 and 3/2011, and 8 age matched controls. MOD was defined by SOFA score obtained at median 8 days (25-75% IQR 7 - 14) postoperatively. SOFA risk was defined as low (≤ 4), medium (5-11) and high (≥12). Purified total RNA was amplified and hybridized on Illumina Whole Transcriptome microarrays. Statistical analysis was conducted on GeneSpring GX 12 using Kruskal-Wallis and adjusted for multiple testing (FDR <0.05, fold change 1.5). Network analysis was done using WGCNA R software.ResultsMean age was 57±15 years. 2444 gene transcripts were differentially expressed between controls and SOFA risk groups. Unsupervised WGCNA (Figure) identified major gene expression modules (Fig 1A) with different degrees of correlation to SOFA score. Comparison of module-characteristic eigengenes (Fig 1B) showed SOFA score was best correlated with the black module, composed of 125 genes (entities). Gene ontology and pathway analysis revealed α-defensins (DEFA1, DEFA3, DEFA4) as the most relevant members of this module, which are multifunctional mediators of innate and adaptive immunity.ConclusionsWCGNA can facilitate identification of key biomarkers of the immune response triggered by MCSD implantation, including a close association between α-defensin pathways and MOD.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S223. DOI:10.1016/j.healun.2013.01.565 · 5.61 Impact Factor
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    ABSTRACT: The presence of coronary lipid early post-HT is evidence of donor atherosclerosis.Methods and Materials30 HT patients underwent coronary angiography and intravascular ultrasound (IVUS) for TCAD screening from a single institution. They received NIRS as part of the COLOR registry after informed consent. NIRS was analyzed for lipid core burden index (LCBI). Linear regression was used to correlate clinical parameters with LCBI. LCBI was subsequently divided into four groups: ≤10, 10-49, 50-100, and >100 and re-analyzed using ordinal regression.ResultsOf the 30 patients, 8 were undergoing routine early screening 30-60 days post-HT (median 40.0, IQR 34.0-47.3 days) and 22 were in the intermediate time range > 60 days (median 406.5, IQR 359.3-732.3 days). 70.6% were male and mean age was 52.5±12.8 years. Total cholesterol was 172.7±38.0, LDL was 93.3±39.5, and HDL was 48.0±14.2 mg/dL. 16.7% had angiographic TCAD, with 3 mild (< 20%), 1 moderate (20-70%), and 1 severe (>70%) disease. 73.1% had intimal thickening by IVUS and 83.3% had lipid plaque by NIRS. For patients with angiographic TCAD, mean LCBI was 47.6±42.2 vs. 26.2±37.9 (p=0.268). For patients with atherosclerosis by IVUS, mean LCBI was 31.6±42.1 vs. 14.9±17.4 (p=0.321). In both unadjusted and multivariate regression, there was no correlation of LCBI with recipient age, gender, hypertension, dyslipidemia, tobacco use, diabetes mellitus, white cell count, LDL, HDL, or cylex level. After dividing LCBI into categories, there was also no correlation to any of these factors.Conclusions The majority of early post-HT patients had lipid burden by NIRS. NIRS appears to be more sensitive than angiography and IVUS in detecting lipid plaque in post-HT patients. The implications of early lipid burden remain unclear post-HT. Longitudinal follow-up is needed to determine if lipid plaque predisposes to development of TCAD.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S209. DOI:10.1016/j.healun.2013.01.520 · 5.61 Impact Factor
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    ABSTRACT: Objectives This retrospective study evaluated the outcomes of patients who underwent unprotected left main coronary artery (ULMCA) percutaneous coronary intervention (PCI) with different types of drug-eluting stents (DES).Background The standard of care for patients with ULMCA is coronary artery bypass surgery. However, current guidelines recommend PCI in clinical conditions where there is an increased risk of adverse surgical outcomes. Clinical outcomes of patients undergoing ULMCA PCI with different types of drug-eluting stents (DES) are unknown.Methods Data from a multicenter international registry, which included 239 consecutive patients from four institutions who ULMCA PCI with DES, were collected.ResultsThere were 42 patients receiving paclitaxel-eluting stent (PES), 158 patients receiving sirolimus-eluting stent (SES), and 39 patients receiving everolimus-eluting stent (EES). There was no statistical difference in major adverse cardiovascular events, cardiac death, myocardial infarction, target lesion revascularization, and stent thrombosis among PES, SES, and EES at 30 days and 1 year.Conclusions There are no differences in clinical events among patients receiving PES, SES, and EES for ULMCA disease.
    Journal of the Saudi Heart Association 04/2013; 25(2):75–78. DOI:10.1016/j.jsha.2013.03.001
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    ABSTRACT: Gender differences in HT outcomes are well known. However, differences in those bridged with LVAD (BTT) have not been well studied. We sought to examine mortality differences in this population.Methods and Materials3020 HT pts BTT (exclusions:<18y, multiorgan, follow up loss) were identified from UNOS (2005-11) & stratified by sex. Survival was censored at 5y. Multivariate Cox proportional hazard regression was adjusted for age, DM, ischemic time, ethnicity, dialysis, life support, wait time & HLA mismatch.ResultsOf 3020 pts, 18% were women. Ischemic (22 & 45%, men(M) & women(F) respectively) & dilated etiologies (69(M) & 49%(F)) were most prevalent. Women were younger & associated with lower BMI, less prior cardiac surgery & better renal function (Table). There was trend towards increased LVAD use in women (p=0.054). Survival (1, 3, 5y) was: F(86, 78, 70%) & M(88, 81, 74%)(Figure). Unadjusted HR for all-cause mortality was 0.85(0.68-1.07,p=0.18). After adjustment: HR 0.86 (0.67-1.11,p<0.67).Conclusions While prior studies have shown increased mortality in women with VADs, we demonstrate that women bridged to HT have similar survival to men post-HT. While there was a trend towards increased LVAD utilization in women, this was not statistically significant. These findings are surprising in light of the availability of the Heartmate II, which permit use in patients with lower BMI.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S173-S174. DOI:10.1016/j.healun.2013.01.414 · 5.61 Impact Factor
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    ABSTRACT: Novel therapies are emerging for treatment of AMR, but minimal data is available comparing efficacy and safety with prevailing treatments. We tested whether the efficacy of bortezomib (Bzb) in lowering donor antibody antibodies (DSA) was improved over standard plasmapheresis (PP)/ IVIG or rituximab therapy for AMR.Methods and MaterialsTen adult heart transplant recipients with DSA mean fluorescence intensity (MFI) >1000, biopsy-proven, and/or clinically suspicious AMR were treated for 20 episodes between February 2010 to August 2012. Treatment consisted of PP (5 days) with IVIG (2 g/kg), rituximab (375 mg/m²), and/or Bzb (0.7-1 mg/m² x 4) at least 30 days apart. Antibody titers were measured via single antigen Luminex® assay before and after therapy. Parametric and non-parametric comparisons, linear and logistic regression were used as appropriate to assess outcomes.ResultsThere was a greater reduction in DSA with Bzb therapy (beta=0.58, 95% CI 0.16-0.90, p=0.01) when adjusting for time to AMR. In those with compromised ejection fraction, there was improvement after Bzb therapy (p=0.03). Patient survival in both groups was 100% at 60 days.Conclusions Compared to PP/IVIG or rituximab, Bzb was more effective in reducing DSA without a significant effect on the incidence of infection or survival in this limited data set. There is indication for a randomized controlled trial comparing Bzb to standard AMR therapies to help determine clinical and survival benefit.Patient Characteristics Other (n=11)Bortezomib (n=10)p-valuePTD at AMR427.9 ± 417.61610.2 ± 2470.40.13DSA MFI at AMR6966.4 ± 5231.27282.0 ± 5874.90.90DSA MFI post-therapy6419.9 ± 4515.55100.8 ± 5754.50.56% MFI decrease0.00 ± 0.370.37 ± 0.520.05Cylex493.7 ± 190.5580.4 ± 159.50.31Allograft Dysfunction36.4%60.0%0.40EMB +72.7%70.0%0.89VAD72.7%60.0%0.66Late AMR36.4%50.0%0.67Infection54.5%50.0%0.84
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S110. DOI:10.1016/j.healun.2013.01.229 · 5.61 Impact Factor
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    ABSTRACT: Outcomes of post-HT patients bridged with ECMO support has not been well studied. We sought to examine these outcomes in a national cohort.Methods and Materials39759 HT recipients were identified from UNOS (1987-2011), of which 115 were bridged with ECMO (Exclusions: age<18, re-HT & lost to follow up). Survival was censored at 12y. Multivariate Cox proportional hazard regression analysis was adjusted for age, sex, DM, race, ischemic time, dialysis, life support, VAD use, wait time & HLA mismatch.ResultsIschemic [41% (ECMO) & 48% (no ECMO)] & dilated [37% (ECMO) & 43% (no ECMO)] cardiomyopathies were the most prevalent. The ECMO cohort was younger (p<0.001) with more prior cardiac surgery (< 0.001) and more status 1 patients (97% vs 72%, p<0.001). ECMO was associated with higher total bilirubin (p=0.001), VAD use (32% vs 17%, p<0.001), ventilator use (46% vs 3%, p<0.001), and dialysis use (6% vs 2%, p<0.001). It was also associated with higher PRA (p<0.001). Survival (1, 5 & 10y) was: ECMO (60, 53, 37% respectively) & non-ECMO (86, 70, 50% respectively) (Figure). Unadjusted HR for all-cause mortality for ECMO was 2.09 (CI 1.60-2.73). Multivariate analysis yielded a HR of 2.11 (CI 1.55-2.86) (p<0.001).Conclusions Survival is poor amongst those bridged with ECMO support. ECMO was associated with worse liver function & increased use of life support. Long-term use of ECMO as bridge should be used cautiously. If further studies support early benefit, there may be utility given apparent stabilization of survival after the early post-HT period.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S141. DOI:10.1016/j.healun.2013.01.318 · 5.61 Impact Factor
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    ABSTRACT: One major function of the 26S proteasome is antigen processing for HLA class I presentation. Following proteasome inhibition with bortezomib (Bzb), one would expect down regulation of class I expression. We explored the differential effect on donor specific and third-party antibodies in Bzb-treated OHT patients. We postulated that compared to class II responses, Bzb is more effective in preventing de novo antibody production to class I alloantigens.Methods and MaterialsPearson correlations among Ab per and across patients were performed for patients receiving Bzb desensitization/AMR therapy from August 2010 to January 2012. Hierarchical clustering was used to find antibody groups of similar response. Treatment consisted of plasmapheresis then Bzb (0.7-1mg/m² IV) on days 1, 4, 7, 10 then a 3-day course of plasmapheresis beginning day 13. Anti-HLA antibody mean fluorescence intensity (MFI) was determined via single antigen Luminex® assay.ResultsEvaluation of the antibody response patterns to Bzb was done on 9 patients. Out of these, 4 patients shared common antibodies, tested multiple times before and after transplantation. Antibody levels are depicted as a heatmap for the intersection of antibody sets. We found that compared to HLA class I locus A and B, HLA class II antibodies demonstrated a significantly decreased response to Bzb. [figure 1]Conclusions We have identified clusters of antibodies with differing degrees of response to Bzb therapy that could be indicative of a class-specific effect. Class I antibodies show a preferential response to bortezomib, while Class II (specifically HLA-DQ) appeared to respond poorly. Our findings suggests that individualized, HLA-specific therapies targeting specific antibody clusters merits further study.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S114. DOI:10.1016/j.healun.2013.01.239 · 5.61 Impact Factor
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    ABSTRACT: Early recognition of MOD has important implications in diagnosis and treatment of patients with advanced heart failure (AdHF) undergoing implantation of mechanical circulatory support devices (MCSD). We hypothesized that whole blood (WB) mRNA gene expression can be linked to systemic inflammatory response as evaluated by SOFA score.Methods and MaterialsWe collected WB from 29 AdHF patients undergoing MCSD implantation between 3/2010 and 5/2011 and 8 age matched controls. MOD was defined by SOFA score, with patients divided into low (≤ 4) (n=8), intermediate (5-11) (n=13), and high (≥12) (n=8) risk groups at median 8 days (IQR 7 - 14) postoperatively. After globin reduction, total mRNA was purified, amplified and hybridized on Illumina Whole Genome Expression Chips. Expression data was extracted and analyzed using GeneSpring GX 12 (Agilent).ResultsMean age was 57±15 years. After normalization with Kruskal-Wallis testing, 440 transcripts were differentially expressed (Figure B) (Benjamini-Hochberg correction, FDR 0.05, fold change 1.5). Hierarchical clustering (A, C) (Pearson absolute distance) organized samples in ascending SOFA risk groups. Gene ontology and pathway analysis revealed significant enrichment of genes representing regulation of immune response including pathways of innate and adaptive immunity. Comparison with PBMC showed >75% overlapping genes (D).ConclusionsWB transcriptome analysis can be used to evaluate the inflammatory response after MCSD. The use of WB without need for PBMC extraction provides a rapid tool that may eventually be performed close to bedside for early prediction of MOD.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S227. DOI:10.1016/j.healun.2013.01.578 · 5.61 Impact Factor

Publication Stats

126 Citations
201.05 Total Impact Points

Institutions

  • 2014
    • CSU Mentor
      Long Beach, California, United States
  • 2013–2014
    • University of Washington Seattle
      • Division of Cardiology
      Seattle, Washington, United States
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
    • Harbor-UCLA Medical Center
      Torrance, California, United States
    • University of Toronto
      • Faculty of Medicine
      Toronto, Ontario, Canada
  • 2009–2013
    • University of California, Los Angeles
      • • Division of Cardiology
      • • Department of Medicine
      Los Ángeles, California, United States
  • 2006–2007
    • Columbia University
      • Department of Biomedical Engineering
      New York, New York, United States