Heart transplantation and human immunodeficiency virus-navigating drug-drug interactions: a case report.

BACKGROUND: Antiretroviral therapy (ART) has led to a decline in human immunodeficiency virus (HIV)-related mortality, but comorbidities, including organ dysfunction, are increasingly the focus of care. Heart transplant (HT) is a very effective therapeutic strategy for end-stage heart failure (HF); however, clinicians may be hesitant due to concerns of complex drug-drug interactions (DDIs) between ART and HT immunosuppressive regimens and the potential impact of ART on long-term HT outcomes. In this report, we describe long-term (76-month) follow-up of a patient with HIV-positive status who underwent orthotopic HT with special emphasis on complex drug interactions. CASE PRESENTATION: A 58-year-old man with HIV-1 developed ischemic cardiomyopathy, progressed to end-stage HF and underwent orthotopic HT. To avoid DDIs with planned immunosuppressive therapies, the ART regimen was modified to consist of lamivudine, tenofovir disoproxil fumarate, rilpivirine, and raltegravir. Following HT, the patient's immunosuppression consisted of tacrolimus and mycophenolate mofetil. He has had normal cardiac function and no opportunistic infections and was subsequently switched to tenofovir alafenamide, emtricitabine, and bictegravir in combination for convenience. Serial HIV-1 RNA blood levels were constantly below the limit of quantification, and his CD4 count remained above 200 cells/mm3 (30-35%). Several DDIs were identified and addressed; however, his long-term post-HT complications included one episode of asymptomatic acute cellular rejection, adenocarcinoma of the prostate, basal cell carcinoma, cardiac allograft vasculopathy, and peripheral neuropathy. CONCLUSION: The clinical outcome of this case supports the conclusion of previously published reports, summarized here within, demonstrating that HIV-1 positive status should not preclude HT in carefully selected individuals. Both addressing potential DDIs prior to HT and long-term monitoring for routine post-transplant complications and secondary and incidental malignancies are imperative.

The Relationship Between Atrial Fibrillation, Mitral Regurgitation, and Heart Failure Subtype: The ARIC Study.

BACKGROUND: Atrial fibrillation (AF) and mitral regurgitation (MR) are closely interrelated in the setting of heart failure (HF). Here we investigate the prevalence and prognostic significance of AF in patients with acute decompensated HF (ADHF) stratified by MR severity. METHODS AND RESULTS: The Atherosclerosis Risk in Communities Study investigated ADHF hospitalizations in residents greater than or equal to 55 years of age in 4 US communities. ADHF cases were stratified by MR severity (none/mild or moderate/severe) and HF subtype (HF with reduced [HFrEF] or preserved [HFpEF] ejection fraction). The odds of AF in patients with increasing MR severity was estimated using multivariable logistic regression, adjusting for age, race, sex, diabetes, hypertension, coronary artery disease, hemodialysis, stroke, and anemia. Cox regression models were used to assess the association of AF with 1-year mortality in patients with HFpEF and HFrEF, stratified by MR severity and adjusted as described, also adjusting for the year of hospitalization. From 2005 to 2014, there were 3,878 ADHF hospitalizations (17,931 weighted). AF was more likely in those with higher MR severity regardless of HF subtype; more so in HFpEF (odds ratio [OR] 1.38, 95% confidence interval [CI], 1.31-1.45) than in HFrEF (OR, 1.19, 95% CI, 1.13-1.25) (interaction P [by HF subtype] < .01). When stratified by HF type, association between AF and 1-year mortality was noted in patients with HFpEF (OR, 1.28, 95% CI 1.04-1.56) but not HFrEF (OR 0.96, 95% CI 0.79-1.16) (interaction by EF subtype, P = .02). CONCLUSIONS: In patients with ADHF, AF prevalence increased with MR severity and this effect was more pronounced in HFpEF compared with HFrEF. AF was associated with an increased 1-year mortality only in patients with HFpEF and concomitant moderate/severe MR. REGISTRATION: NCT00005131, https://clinicaltrials.gov/ct2/show/NCT00005131.

Factors Associated With Cognitive Impairment in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Cognitive impairment is prevalent in heart failure and is associated with higher mortality rates. The mechanism behind cognitive impairment in heart failure with preserved ejection fraction (HFpEF) has not been established. OBJECTIVE: The aim of this study was to evaluate associations between abnormal cardiac hemodynamics and cognitive impairment in individuals with HFpEF. METHODS: A secondary analysis of Atherosclerosis Risk in Communities (Atherosclerosis Risk in Communities) study data was performed. Participants free of stroke or dementia who completed in-person assessments at visit 5 were included. Neurocognitive test scores among participants with HFpEF, heart failure with reduced ejection fraction (HFrEF), and no heart failure were compared. Sociodemographics, comorbid illnesses, medications, and echocardiographic measures of cardiac function that demonstrated significant (P < .10) bivariate associations with neurocognitive test scores were included in multivariate models to identify predictors of neurocognitive test scores among those with HFpEF. Multiple imputation by chained equations was used to account for missing values. RESULTS: Scores on tests of attention, language, executive function, and global cognitive function were worse among individuals with HFpEF than those with no heart failure. Neurocognitive test scores were not significantly different among participants with HFpEF and HFrEF. Worse diastolic function was weakly associated with worse performance in memory, attention, and language. Higher cardiac index was associated with worse performance on 1 test of attention. CONCLUSIONS: Cognitive impairment is prevalent in HFpEF and affects several cognitive domains. The current study supports the importance of cognitive screening in patients with heart failure. An association between abnormal cardiac hemodynamics and cognitive impairment was observed, but other factors are likely involved.

Temporal Trends in Prevalence and Prognostic Implications of Comorbidities Among Patients With Acute Decompensated Heart Failure: The ARIC Study Community Surveillance.

BACKGROUND: Patients with heart failure (HF) have multiple coexisting comorbidities. The temporal trends in the burden of comorbidities and associated risk of mortality among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not well established. METHODS: HF-related hospitalizations were sampled by stratified design from 4 US areas in 2005 to 2014 by the community surveillance component of the ARIC study (Atherosclerosis Risk in Communities). Acute decompensated HF was classified by standardized physician review and a previously validated algorithm. An ejection fraction <50% was considered HFrEF. A total of 15 comorbidities were abstracted from the medical record. Mortality outcomes were ascertained for up to 1-year postadmission by linking hospital records with death files. RESULTS: A total of 5460 hospitalizations (24 937 weighted hospitalizations) classified as acute decompensated HF had available ejection fraction data (53% female, 68% white, 53% HFrEF, 47% HFpEF). The average number of comorbidities was higher for patients with HFpEF versus HFrEF, both for women (5.53 versus 4.94; P<0.0001) and men (5.20 versus 4.82; P<0.0001). There was a significant temporal increase in the overall burden of comorbidities, both for patients with HFpEF (women: 5.17 in 2005-2009 to 5.87 in 2010-2013; men: 4.94 in 2005-2009 and 5.45 in 2010-2013) and HFrEF (women: 4.78 in 2005-2009 to 5.14 in 2010-2013; men: 4.62 in 2005-2009 and 5.06 in 2010-2013; P-trend<0.0001 for all). Higher comorbidity burden was significantly associated with higher adjusted risk of 1-year mortality, with a stronger association noted for HFpEF (hazard ratio [HR] per 1 higher comorbidity, 1.19 [95% CI, 1.14-1.25] versus HFrEF (HR, 1.10 [95% CI, 1.05-1.14]; P for interaction by HF type=0.02). The associated mortality risk per 1 higher comorbidity also increased significantly over time for patients with HFpEF and HFrEF, as well (P for interaction with time=0.002 and 0.02, respectively) Conclusions: The burden of comorbidities among hospitalized patients with acute decompensated HFpEF and HFrEF has increased over time, as has its associated mortality risk. Higher burden of comorbidities is associated with higher risk of mortality, with a stronger association noted among patients with HFpEF versus HFrEF.

Cardiac Amyloidosis: Evolving Diagnosis and Management: A Scientific Statement From the American Heart Association.

Transthyretin amyloid cardiomyopathy (ATTR-CM) results in a restrictive cardiomyopathy caused by extracellular deposition of transthyretin, normally involved in the transportation of the hormone thyroxine and retinol-binding protein, in the myocardium. Enthusiasm about ATTR-CM has grown as a result of 3 simultaneous areas of advancement: Imaging techniques allow accurate noninvasive diagnosis of ATTR-CM without the need for confirmatory endomyocardial biopsies; observational studies indicate that the diagnosis of ATTR-CM may be underrecognized in a significant proportion of patients with heart failure; and on the basis of elucidation of the mechanisms of amyloid formation, therapies are now approved for treatment of ATTR-CM. Because therapy for ATTR-CM may be most effective when administered before significant cardiac dysfunction, early identification of affected individuals with readily available noninvasive tests is essential. This scientific statement is intended to guide clinical practice and to facilitate management conformity by covering current diagnostic and treatment strategies, as well as unmet needs and areas of active investigation in ATTR-CM.

Association of Midlife Cardiovascular Risk Factors With the Risk of Heart Failure Subtypes Later in Life.

BACKGROUND: Independent associations between cardiovascular risk factor exposures during midlife and later life development of heart failure (HF) with preserved ejection fraction (HFpEF) versus reduced EF (HFrEF) have not been previously studied. METHODS: We pooled data from 4 US cohort studies (Atherosclerosis Risk in Communities, Cardiovascular Health, Health , Aging and Body Composition, and Multi-Ethnic Study of Atherosclerosis) and imputed annual risk factor trajectories for body mass index, systolic and diastolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol, and glucose starting from age 40 years. Time-weighted average exposures to each risk factor during midlife and later life were calculated and analyzed for associations with the development of HFpEF or HFrEF. RESULTS: A total of 23,861 participants were included (mean age at first in-person visit, 61.8 ±1 0.2 years; 56.6% female). During a median follow-up of 12 years, there were 3666 incident HF events, of which 51% had EF measured, including 934 with HFpEF and 739 with HFrEF. A high midlife systolic blood pressure and low midlife high-density lipoprotein cholesterol were associated with HFrEF, and a high midlife body mass index, systolic blood pressure, pulse pressure, and glucose were associated with HFpEF. After adjusting for later life exposures, only midlife pulse pressure remained independently associated with HFpEF. CONCLUSIONS: Midlife exposure to cardiovascular risk factors are differentially associated with HFrEF and HFpEF later in life. Having a higher pulse pressure during midlife is associated with a greater risk for HFpEF but not HFrEF, independent of later life exposures.

Sensitization in Heart Transplantation: Emerging Knowledge: A Scientific Statement From the American Heart Association.

Sensitization, defined as the presence of circulating antibodies, presents challenges for heart transplant recipients and physicians. When present, sensitization can limit a transplantation candidate's access to organs, prolong wait time, and, in some cases, exclude the candidate from heart transplantation altogether. The management of sensitization is not yet standardized, and current therapies have not yielded consistent results. Although current strategies involve antibody suppression and removal with intravenous immunoglobulin, plasmapheresis, and antibody therapy, newer strategies with more specific targets are being investigated.

Trends in Hospitalizations and Survival of Acute Decompensated Heart Failure in Four US Communities (2005-2014): ARIC Study Community Surveillance.

BACKGROUND: Community trends of acute decompensated heart failure (ADHF) in diverse populations may differ by race and sex. METHODS: The ARIC study (Atherosclerosis Risk in Communities) sampled heart failure-related hospitalizations (≥55 years of age) in 4 US communities from 2005 to 2014 using International Classification of Diseases, Ninth Revision, Clinical Modification codes. ADHF hospitalizations were validated by standardized physician review and computer algorithm, yielding 40 173 events after accounting for sampling design (unweighted n=8746). RESULTS: Of the ADHF hospitalizations, 50% had reduced ejection fraction, and 39% had preserved EF (HFpEF). HF with reduced ejection fraction was more common in black men and white men, whereas HFpEF was most common in white women. Average age-adjusted rates of ADHF were highest in blacks (38.1 per 1000 black men, 30.5 per 1000 black women), with rates differing by HF type and sex. ADHF rates increased over the 10 years (average annual percentage change: black women +4.3%, black men +3.7%, white women +1.9%, white men +2.6%), mostly reflecting more acute HFpEF. Age-adjusted 28-day and 1-year case fatality proportions were ≈10% and 30%, respectively, similar across race-sex groups and HF types. Only blacks showed decreased 1-year mortality over time (average annual percentage change: black women -5.4%, black men -4.6%), with rates differing by HF type (average annual percentage change: black women HFpEF -7.1%, black men HF with reduced ejection fraction -4.7%). CONCLUSIONS: Between 2005 and 2014, trends in ADHF hospitalizations increased in 4 US communities, primarily driven by acute HFpEF. Survival at 1 year was poor regardless of EF but improved over time for black women and black men.

Desensitization for sensitized patients awaiting heart transplant.

PURPOSE OF REVIEW: This review summarizes contemporary desensitization strategies for patients awaiting cardiac transplantation in an era when specific management is still somewhat controversial. RECENT FINDINGS: The number of sensitized patients awaiting heart transplantation is rising. Clinical assessment of antibody levels is mostly focused on human leukocyte antigen (HLA) antibodies. Sensitization to HLA antigens increases the risk of antibody medicated rejection and cardiac allograft vasculopathy after transplant, thus translates to reduced access to compatible donors and increased wait time to transplant. Desensitization therapy is commonly considered in listed patients with cPRA more than 50%, to either decrease the amount of circulating anti-HLA antibodies, reduce the antibody production, or a combination of both. Despite promising results on specific therapies (e.g., plasmapheresis, intravenous immunoglobulin, rituximab, bortezomib), there is a significant gap in knowledge on desensitization therapies in heart transplantation. Most data are from small observational studies and extrapolated from nonheart solid organ transplants. SUMMARY: Management of the sensitized patient awaiting heart transplant is individualized. Desensitization can facilitate negative cross-match and successful transplantation, but is associated with significant cost and potential adverse effects. The long-term outcomes of desensitization therapy remain to be determined, further emphasizing the importance of personalizing the treatment approach to each patient.

Heart Failure Stages Among Older Adults in the Community: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Although heart failure (HF) disproportionately affects older adults, little data exist regarding the prevalence of American College of Cardiology/American Heart Association HF stages among older individuals in the community. Additionally, the role of contemporary measures of longitudinal strain and diastolic dysfunction in defining HF stages is unclear. METHODS: HF stages were classified in 6118 participants in the Atherosclerosis Risk in Communities study (67-91 years of age) at the fifth study visit as follows: A (asymptomatic with HF risk factors but no cardiac structural or functional abnormalities), B (asymptomatic with structural abnormalities, defined as left ventricular hypertrophy, dilation or dysfunction, or significant valvular disease), C1 (clinical HF without prior hospitalization), and C2 (clinical HF with earlier hospitalization). RESULTS: Using the traditional definitions of HF stages, only 5% of examined participants were free of HF risk factors or structural heart disease (Stage 0), 52% were categorized as Stage A, 30% Stage B, 7% Stage C1, and 6% Stage C2. Worse HF stage was associated with a greater risk of incident HF hospitalization or death at a median follow-up of 608 days. Left ventricular (LV) ejection fraction was preserved in 77% and 65% in Stages C1 and C2, respectively. Incorporation of longitudinal strain and diastolic dysfunction into the Stage B definition reclassified 14% of the sample from Stage A to B and improved the net reclassification index (P=0.028) and integrated discrimination index (P=0.016). Abnormal LV structure, systolic function (based on LV ejection fraction and longitudinal strain), and diastolic function (based on e', E/e', and left atrial volume index) were each independently and additively associated with risk of incident HF hospitalization or death in Stage A and B participants. CONCLUSIONS: The majority of older adults in the community are at risk for HF (Stages A or B), appreciably more compared with previous reports in younger community-based samples. LV ejection fraction is robustly preserved in at least two-thirds of older adults with prevalent HF (Stage C), highlighting the burden of HF with preserved LV ejection fraction in the elderly. LV diastolic function and longitudinal strain provide incremental prognostic value beyond conventional measures of LV structure and LV ejection fraction in identifying persons at risk for HF hospitalization or death.

Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report.

The presence of preexisting (memory) or de novo donor-specific HLA antibodies (DSAs) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding of histocompatibility have advanced significantly in recent years, the criteria to define presence of a DSA and assign a level of risk for a given DSA vary markedly between centers. A collaborative effort between the American Society for Histocompatibility and Immunogenetics and the American Society of Transplantation provided the logistical support for generating a dedicated multidisciplinary working group, which included experts in histocompatibility as well as kidney, liver, heart, and lung transplantation. The goals were to perform a critical review of biologically driven, state-of-the-art, clinical diagnostics literature and to provide clinical practice recommendations based on expert assessment of quality and strength of evidence. The results of the Sensitization in Transplantation: Assessment of Risk (STAR) meeting are summarized here, providing recommendations on the definition and utilization of HLA diagnostic testing, and a framework for clinical assessment of risk for a memory or a primary alloimmune response. The definitions, recommendations, risk framework, and highlighted gaps in knowledge are intended to spur research that will inform the next STAR Working Group meeting in 2019.

Heart Failure and Cognitive Impairment in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Previous studies suggest that heart failure (HF) is an independent risk factor for cognitive decline. A better understanding of the relationship between HF, cognitive status, and cognitive decline in a community-based sample may help clinicians understand disease risk. OBJECTIVE: To examine whether persons with HF have a higher prevalence of cognitive impairment and whether persons developing HF have more rapid cognitive decline. DESIGN: This observational cohort study of American adults in the Atherosclerosis Risk in Communities (ARIC) study has two components: cross-sectional analysis examining the association between prevalent HF and cognition using multinomial logistic regression, and change over time analysis detailing the association between incident HF and change in cognition over 15 years. PARTICIPANTS: Among visit 5 (2011-2013) participants (median age 75 years), 6495 had neurocognitive information available for cross-sectional analysis. Change over time analysis examined the 5414 participants who had cognitive scores and no prevalent HF at visit 4 (1996-1998). MEASUREMENTS: The primary outcome was cognitive status, classified as normal, mild cognitive impairment [MCI], and dementia on the basis of standardized cognitive tests (delayed word recall, word fluency, and digit symbol substitution). Cognitive change was examined over a 15-year period. Control variables included socio-demographic, vascular, and smoking/drinking measures. RESULTS: At visit 5, participants with HF had a higher prevalence of dementia (adjusted relative risk ratio [RRR] = 1.60 [95% CI 1.13, 2.25]) and MCI (RRR = 1.36 [1.12, 1.64]) than those without HF. A decline in cognition between visits 4 and 5 was - 0.07 standard deviation units [- 0.13, - 0.01] greater among persons who developed HF compared to those who did not. Results did not differ by ejection fraction. CONCLUSION: HF is associated with neurocognitive dysfunction and decline independent of other co-morbid conditions. Further study is needed to determine the underlying pathophysiology.

A case-control study of the risk factors for developing aspergillosis following cardiac transplant.

BACKGROUND: Invasive aspergillosis (IA) is a significant cause of morbidity and mortality following cardiac transplantation; however, data regarding the predictors of IA in this patient population are limited. METHODS: We conducted a case-control study to identify the risk factors for IA in patients who underwent cardiac transplantation at a single center from 1986 to 2008 (Cohort 1) and 2009 to 2015 (Cohort 2). Cases of IA were matched to two controls from the same year of transplantation, and data were collected from the date of cardiac transplantation to the date of documented Aspergillus infection for each case, or for an equivalent number of days for each control. Univariate and multivariate logistic regressions were used to identify independent predictors of IA in Cohort 1. After 2009, targeted antifungal prophylaxis with oral voriconazole was initiated in patients with risk factors for IA. The incidence of IA was compared pre- and postintervention. RESULTS: IA was identified in 23 of 189 (8.0%) patients within Cohort 1. Significant risk factors for IA on multivariate analysis included an increased number of pretransplant hospitalizations (OR 1.81, 95% CI 1.19-2.76) and posttransplant acute cellular allograft rejection (ACR) (OR 1.99, 95% 1.06-3.75). Following the implementation of targeted antifungal prophylaxis in 2009, IA was identified in 2 of 107 (2.0%) patients in Cohort 2. CONCLUSIONS: Increased pretransplant hospitalizations and posttransplant ACR episodes represent significant risk factors for IA following cardiac transplant. Targeted antifungal prophylaxis in at-risk patients reduces the incidence of IA.

The Loss of GSTM1 Associates with Kidney Failure and Heart Failure.

Glutathione S-transferase mu 1 (GSTM1) encodes an enzyme that catalyzes the conjugation of electrophilic compounds with glutathione to facilitate their degradation or excretion. The loss of one or both copies of GSTM1 is common in many populations and has been associated with CKD progression. With the hypothesis that the loss of GSTM1 is also associated with incident kidney failure and heart failure, we estimated GSTM1 copy number using exome sequencing reads in the Atherosclerosis Risk in Communities (ARIC) Study, a community-based prospective cohort of white and black participants. Overall, 51.2% and 39.8% of white participants and 25.6% and 48.5% of black participants had zero or one copy of GSTM1, respectively. Over a median follow-up of 24.6 years, 256 kidney failure events occurred in 5715 participants without prevalent kidney failure, and 1028 heart failure events occurred in 5368 participants without prevalent heart failure. In analysis adjusted for demographics, diabetes, and hypertension, having zero or one copy of GSTM1 associated with higher risk of kidney failure and heart failure (adjusted hazard ratio [95% confidence interval] for zero or one versus two copies of GSTM1: kidney failure, 1.66 [1.27 to 2.17]; heart failure, 1.16 [1.04 to 1.29]). Risk did not differ significantly between participants with zero and one copy of GSTM1 (P>0.10). In summary, the loss of GSTM1 was significantly associated with incident kidney and heart failure, independent of traditional risk factors. These results suggest GSTM1 function is a potential treatment target for the prevention of kidney and heart failure.

Incident Heart Failure and Cognitive Decline: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Cognitive impairment is found in a significant proportion of patients with heart failure (HF). Although cognitive impairment may be a consequence of HF, early signs of cognitive impairment may also indicate subclinical vascular disease, and thus a risk factor for future cardiovascular events. METHODS AND RESULTS: The Atherosclerosis Risk in Communities Study is a prospective cohort study of the development of atherosclerosis. Cox proportional hazards regression was used to examine the association between mean 6-year change in cognitive function and incident HF in 7962 white and 1933 African-American men and women aged 46 to 70 years and free of clinical stroke. Scores were obtained for the Delayed Word Recall Test, the Digit Symbol Substitution Test (DSST), and the Word Fluency Test. There was a significantly increased risk of developing HF during the mean 12.6-year follow-up period after adjustment for age, gender, race, and education for those in the quartile with the greatest decline in DSST scores (hazard ratio [HR] = 1.17, P = .009), and in the quartile with the lowest baseline DSST scores (HR = 1.43, P < .001). CONCLUSIONS: The results suggest that relatively low performance on a test of information processing speed may serve as an indicator of HF risk in middle age.

Temporal Trends in Hospitalization for Acute Decompensated Heart Failure in the United States, 1998-2011.

Estimates of the numbers and rates of acute decompensated heart failure (ADHF) hospitalization are central to understanding health-care utilization and efforts to improve patient care. We comprehensively estimated the frequency, rate, and trends of ADHF hospitalization in the United States. Based on Atherosclerosis Risk in Communities (ARIC) Study surveillance adjudicating 12,450 eligible hospitalizations during 2005-2010, we developed prediction models for ADHF separately for 3 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 428 discharge diagnosis groups: 428 primary, 428 nonprimary, or 428 absent. We applied the models to data from the National Inpatient Sample (11.5 million hospitalizations of persons aged ≥55 years with eligible ICD-9-CM codes), an all-payer, 20% probability sample of US community hospitals. The average estimated number of ADHF hospitalizations per year was 1.76 million (428 primary, 0.80 million; 428 nonprimary, 0.83 million; 428 absent, 0.13 million). During 1998-2004, the rate of ADHF hospitalization increased by 2.0%/year (95% confidence interval (CI): 1.8, 2.5) versus a 1.4%/year (95% CI: 0.8, 2.1) increase in code 428 primary hospitalizations (P < 0.001). In contrast, during 2005-2011, numbers of ADHF hospitalizations were stable (-0.5%/year; 95% CI: -1.4, 0.3), while the numbers of 428-primary hospitalizations decreased by -1.5%/year (95% CI: -2.2, -0.8) (P for contrast = 0.03). In conclusion, the estimated number of hospitalizations with ADHF is approximately 2 times higher than the number of hospitalizations with ICD-9-CM code 428 in the primary position. The trend increased more steeply prior to 2005 and was relatively flat after 2005.

Reactive hyperemia is associated with adverse clinical outcomes in heart failure.

INTRODUCTION: Impaired endothelial function, as assessed by brachial artery flow-mediated dilation (FMD), is an established risk factor for cardiovascular events. FMD is impaired in heart failure (HF) patients, but less is known about hyperemic brachial artery flow. We investigated the relationship between FMD and hyperemic flow with adverse clinical outcomes in HF patients. METHODS: Brachial artery FMD and hyperemic flow were assessed in 156 patients (70.5 % Male; 45.5% Caucasian; mean age (± SD) = 56.2 (±12.4) years) with HF and reduced left ventricular ejection fraction (LVEF). Cox proportional hazard models were used to assess the potential explanatory association of FMD and hyperemic flow with the composite outcome of death or cardiovascular hospitalization over a median 5-year follow-up period. RESULTS: Both FMD and hyperemic flow were negatively correlated with age, but unrelated to sex, race, body mass index, LVEF or N-terminal pro-B-Type natriuretic peptide (NT-ProBNP). Reduced hyperemic flow, but not FMD, was associated with an increased risk of death or cardiac hospitalization after controlling for traditional risk factors. CONCLUSION: The association of reduced hyperemic flow with increased risk of adverse clinical outcomes suggests that micro-vascular function may be an important prognostic marker in patients with HF.

Anger proneness, gender, and the risk of heart failure.

BACKGROUND: Evidence regarding the association of anger proneness with incidence of heart failure is lacking. METHODS AND RESULTS: Anger proneness was ascertained among 13,171 black and white participants of the Atherosclerosis Risk in Communities (ARIC) study cohort with the use of the Spielberger Trait Anger Scale. Incident heart failure events, defined as occurrence of ICD-9-CM code 428.x, were ascertained from participants' medical records during follow-up in the years 1990-2010. Relative hazard of heart failure across categories of trait anger was estimated with the use of Cox proportional hazard models. Study participants (mean age 56.9 [SD 5.7] years) experienced 1,985 incident HF events during 18.5 (SD 4.9) years of follow-up. Incidence of HF was greater among those with high, as compared to those with low or moderate trait anger, with higher incidence observed for men than for women. The relative hazard of incident HF was modestly high among those with high trait anger, compared with those with low or moderate trait anger (age-adjusted hazard ratio for men: 1.44 (95% confidence interval [CI] 1.23-1.69). Adjustment for comorbidities and depressive symptoms attenuated the estimated age-adjusted relative hazard in men to 1.26 (95% CI 1.00-1.60). CONCLUSIONS: Assessment of anger proneness may be necessary in successful prevention and clinical management of heart failure, especially in men.

The role of heart failure pharmacotherapy after left ventricular assist device support.

Left ventricular assist devices (LVADs) are an increasingly common treatment for end-stage systolic heart failure. However, there are limited data on how to best treat patients pharmacologically after LVAD implantation, resulting in uncertainty about which heart failure medications provide the most benefit. Still, some evidence exists that certain medical therapies can prevent remodeling and improve right ventricular and, possibly, left ventricular function. This article reviews the current literature for medical heart failure therapy in LVAD patients, and possible future treatment strategies.