Chi-Hong Tseng

Temporal Trends in Treatment and Outcomes for Advanced Heart Failure with Reduced Ejection Fraction from 1993-2010: Findings from a University Referral Center

Background—Randomized trials have demonstrated the efficacy of several new therapies for heart failure (HF) with reduced ejection fraction over the preceding 2 decades. This study investigates whether these therapeutic advances have translated into improvement in outcomes for patients with advanced HF referred to a heart transplant center. Methods and Results—Patients with HF (n=2507) referred to a single university center were analyzed in three 6-year eras during which medical and device therapies were evolving: 1993 to 1998 (era 1), 1999 to 2004 (era 2), and 2005 to 2010 (era 3). Impaired hemodynamics and comorbidities were more frequent at time of referral in later eras, whereas other HF severity parameters where similar or improved. Successive eras had greater usage of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, &bgr;-blockers, aldosterone antagonists, implantable cardioverter defibrillators, and cardiac resynchronization therapy, consistent with evolving evidence and guideline recommendations over the study period. All-cause mortality and sudden death were significantly lower in era 2 and 3 compared with era 1. After multivariable risk adjustment, era 3 had significantly decreased 2- and 3-year all-cause mortality risk and significantly decreased 1- and 3-year sudden death risk compared with era 1. However, progressive HF death and the combined outcome of mortality/urgent transplant/ventricular assist device were modestly increased in the latter eras. Conclusions—Over the past 2 decades, patients with advanced HF referred to and managed at a tertiary university referral center have benefited from advances in HF medications and devices, as evidenced by improvements in overall survival and sudden death risk.

Performance of the Pooled Cohort atherosclerotic cardiovascular disease risk score in hepatitis C virus-infected persons

Chronic hepatitis C virus (HCV) infection has been associated with an increased risk for cardiovascular disease (CVD). The recommended Pooled Cohort atherosclerotic cardiovascular disease (ASCVD) risk equation for estimation of 10‐year CVD risk has not been validated in HCV‐infected populations. We examined the performance of the ASCVD risk score in HCV‐infected persons, using the national Electronically Retrieved Cohort of HCV Infected Veterans to derive a cohort of HCV‐infected and uninfected subjects without baseline ASCVD, hepatitis B, or HIV infection, and with low‐density lipoprotein cholesterol level<190 mg/dL. Performance of the ASCVD risk equation was assessed by Cox proportional hazard regression, C‐statistics and Hosmer‐Lemeshow statistic. The cohort included 70 490 HCV‐infected and 97 766 HCV‐uninfected men with mean age of 55 years, 56% White and 29% Black. Incident CVD event rates were similar between the two groups (13.2 and 13.4 events/1000 person‐years), with a higher incidence of coronary heart disease events in the HCV‐uninfected group and of stroke events in the HCV‐infected group. Adjusting for ASCVD risk score, HCV infection was associated with higher risk for an ASCVD event in the subgroup with baseline ASCVD risk ≥7.5% (HR: 1.19, P<.0001). C‐statistics were poor in both the HCV‐infected and uninfected groups (0.60 and 0.61, respectively). By Hosmer‐Lemeshow test, the ASCVD risk equation overestimated risk amongst lower risk patients and underestimated risk amongst higher risk patients in both the HCV‐infected and uninfected groups. Further investigation is needed to determine whether a modified equation to accurately predict ASCVD risk in HCV‐infected persons is warranted.

Clinical phenomapping and outcomes after heart transplantation

BACKGROUNDnSurvival after heart transplantation (HTx) is limited by complications related to alloreactivity, immune suppression, and adverse effects of pharmacologic therapies. We hypothesize that time-dependent phenomapping of clinical and molecular data sets is a valuable approach to clinical assessments and guiding medical management to improve outcomes.nnnMETHODSnWe analyzed clinical, therapeutic, biomarker, and outcome data from 94 adult HTx patients and 1,557 clinical encounters performed between January 2010 and April 2013. Multivariate analyses were used to evaluate the association between immunosuppression therapy, biomarkers, and the combined clinical end point of death, allograft loss, retransplantation, and rejection. Data were analyzed by K-means clustering (K = 2) to identify patterns of similar combined immunosuppression management, and percentile slopes were computed to examine the changes in dosages over time. Findings were correlated with clinical parameters, human leucocyte antigen antibody titers, and peripheral blood mononuclear cell gene expression of the AlloMap (CareDx, Inc., Brisbane, CA) test genes. An intragraft, heart tissue gene coexpression network analysis was performed.nnnRESULTSnUnsupervised cluster analysis of immunosuppressive therapies identified 2 groups, 1 characterized by a steeper immunosuppression minimization, associated with a higher likelihood for the combined end point, and the other by a less pronounced change. A time-dependent phenomap suggested that patients in the group with higher event rates had increased human leukocyte antigen class I and II antibody titers, higher expression of the FLT3 AlloMap gene, and lower expression of the MARCH8 and WDR40A AlloMap genes. Intramyocardial biomarker-related coexpression network analysis of the FLT3 gene showed an immune system-related network underlying this biomarker.nnnCONCLUSIONSnTime-dependent precision phenotyping is a mechanistically insightful, data-driven approach to characterize patterns of clinical care and identify ways to improve clinical management and outcomes.

Attitudes and potential barriers towards hepatitis C treatment in patients with and without HIV coinfection

This study aimed to assess attitudes and potential barriers towards treatment in patients with hepatitis C virus (HCV) infection, comparing those with and without HIV coinfection. A cross-sectional survey of 82 HCV-infected adults with and without HIV was conducted in greater Los Angeles between November 2013 and July 2015. Overall, there were 53 (64.6%) with HIV coinfection, 20 (25.0%) with self-reported cirrhosis, and 22 (26.8%) with a history of prior HCV treatment. Of all, 93.2% wanted HCV treatment, but 45.9% were unwilling/unable to spend anything out of pocket, 29.4% were waiting for new therapies, and 23.5% were recommended to defer HCV treatment. HIV/HCV-coinfected patients were more likely to want treatment within one year (90.2% versus 68.2%, pu2009=u20090.02), more willing to join a clinical trial (74.5% versus 8.0%, pu2009<u20090.01), more willing to take medications twice daily (86.3% versus 61.5%, pu2009=u20090.01), and more likely to prefer hepatitis C treatment by an infectious diseases/HIV physician (36.7% versus 4.0%, pu2009<u20090.01). Of all, 77.1% of coinfected patients were willing to change antiretroviral therapy if necessary to treat HCV, but only 48.0% of patients were willing to take a medication if it had not been studied in HIV-positive patients. Treatment preferences differ between HIV/HCV-coinfected and HCV-monoinfected patients. Despite a strong willingness among the study cohort to start HCV treatment, other factors such as cost, access to medications, and provider reluctance may be delaying treatment initiation.

Viral Pneumonia Accelerates Graft Death and CLAD in Lung Transplant Recipients

s S305 with any CARV infection (HR 1.79, p < 0.01), though when analyzed as parallel predictors in subgroup analysis, only clinical pneumonia remained statistically significant (HR 1.64, p = 0.03). Asymptomatic viral infection (HR 1.50, p = 0.08) and symptomatic viral infection (HR 1.03, p = 0.91) did not meet statistical significance. Viral pneumonia significantly increased the risk of graft death (HR 2.58, p < 0.01). However, overall CARV infection (HR 0.92, p = 0.60), asymptomatic CARV infection (HR 0.76, p = 0.24), and symptomatic CARV infection (HR 0.78, p = 0.42) did not. Conclusion: Viral pneumonia increases the risk of graft death and CLAD after lung transplantation. Overall CARV infections also appear to increase the risk of CLAD, although in our cohort this risk was primarily driven by those with viral pneumonia. Asymptomatic viral carriage and symptomatic CARV infection without pneumonia did not appear to impact graft survival.

Temporal Trends in Treatment and Outcomes for Advanced Heart Failure With Reduced Ejection Fraction From 1993–2010Clinical Perspective

Background—Randomized trials have demonstrated the efficacy of several new therapies for heart failure (HF) with reduced ejection fraction over the preceding 2 decades. This study investigates whether these therapeutic advances have translated into improvement in outcomes for patients with advanced HF referred to a heart transplant center. Methods and Results—Patients with HF (n=2507) referred to a single university center were analyzed in three 6-year eras during which medical and device therapies were evolving: 1993 to 1998 (era 1), 1999 to 2004 (era 2), and 2005 to 2010 (era 3). Impaired hemodynamics and comorbidities were more frequent at time of referral in later eras, whereas other HF severity parameters where similar or improved. Successive eras had greater usage of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, &bgr;-blockers, aldosterone antagonists, implantable cardioverter defibrillators, and cardiac resynchronization therapy, consistent with evolving evidence and guideline recommendations over the study period. All-cause mortality and sudden death were significantly lower in era 2 and 3 compared with era 1. After multivariable risk adjustment, era 3 had significantly decreased 2- and 3-year all-cause mortality risk and significantly decreased 1- and 3-year sudden death risk compared with era 1. However, progressive HF death and the combined outcome of mortality/urgent transplant/ventricular assist device were modestly increased in the latter eras. Conclusions—Over the past 2 decades, patients with advanced HF referred to and managed at a tertiary university referral center have benefited from advances in HF medications and devices, as evidenced by improvements in overall survival and sudden death risk.

Temporal Trends in Treatment and Outcomes for Advanced Heart Failure With Reduced Ejection Fraction From 1993–2010Clinical Perspective: Findings From a University Referral Center

Background—Randomized trials have demonstrated the efficacy of several new therapies for heart failure (HF) with reduced ejection fraction over the preceding 2 decades. This study investigates whether these therapeutic advances have translated into improvement in outcomes for patients with advanced HF referred to a heart transplant center. Methods and Results—Patients with HF (n=2507) referred to a single university center were analyzed in three 6-year eras during which medical and device therapies were evolving: 1993 to 1998 (era 1), 1999 to 2004 (era 2), and 2005 to 2010 (era 3). Impaired hemodynamics and comorbidities were more frequent at time of referral in later eras, whereas other HF severity parameters where similar or improved. Successive eras had greater usage of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, &bgr;-blockers, aldosterone antagonists, implantable cardioverter defibrillators, and cardiac resynchronization therapy, consistent with evolving evidence and guideline recommendations over the study period. All-cause mortality and sudden death were significantly lower in era 2 and 3 compared with era 1. After multivariable risk adjustment, era 3 had significantly decreased 2- and 3-year all-cause mortality risk and significantly decreased 1- and 3-year sudden death risk compared with era 1. However, progressive HF death and the combined outcome of mortality/urgent transplant/ventricular assist device were modestly increased in the latter eras. Conclusions—Over the past 2 decades, patients with advanced HF referred to and managed at a tertiary university referral center have benefited from advances in HF medications and devices, as evidenced by improvements in overall survival and sudden death risk.