Caregiver Health-Related Quality of Life, Burden, and Patient Outcomes in Ambulatory Advanced Heart Failure: A Report From REVIVAL.

Background Heart failure (HF) imposes significant burden on patients and caregivers. Longitudinal data on caregiver health-related quality of life (HRQOL) and burden in ambulatory advanced HF are limited. Methods and Results Ambulatory patients with advanced HF (n=400) and their participating caregivers (n=95) enrolled in REVIVAL (Registry Evaluation of Vital Information for VADs [Ventricular Assist Devices] in Ambulatory Life) were followed up for 24 months, or until patient death, left ventricular assist device implantation, heart transplantation, or loss to follow-up. Caregiver HRQOL (EuroQol Visual Analog Scale) and burden (Oberst Caregiving Burden Scale) did not change significantly from baseline to follow-up. At time of caregiver enrollment, better patient HRQOL by Kansas City Cardiomyopathy Questionnaire was associated with better caregiver HRQOL (P=0.007) and less burden by both time spent (P<0.0001) and difficulty (P=0.0007) of caregiving tasks. On longitudinal analyses adjusted for baseline values, better patient HRQOL (P=0.034) and being a married caregiver (P=0.016) were independently associated with better caregiver HRQOL. Patients with participating caregivers (versus without) were more likely to prefer left ventricular assist device therapy over time (odds ratio, 1.43; 95% CI, 1.03-1.99; P=0.034). Among patients with participating caregivers, those with nonmarried (versus married) caregivers were at higher composite risk of HF hospitalization, death, heart transplantation or left ventricular assist device implantation (hazard ratio, 2.99; 95% CI, 1.29-6.96; P=0.011). Conclusions Patient and caregiver characteristics may impact their HRQOL and other health outcomes over time. Understanding the patient-caregiver relationship may better inform medical decision making and outcomes in ambulatory advanced HF.

Racial Differences and Temporal Obesity Trends in Heart Failure with Preserved Ejection Fraction.

BACKGROUND/OBJECTIVES: Obesity increases with age, is disproportionately prevalent in black populations, and is associated with heart failure with preserved ejection fraction (HFpEF). An "obesity paradox," or improved survival with obesity, has been reported in patients with HFpEF. The aim of this study was to examine whether racial differences exist in the temporal trends and outcomes associated with obesity among older patients with HFpEF. DESIGN: Community surveillance of acute decompensated heart failure (ADHF) hospitalizations, sampled by stratified design from 2005 to 2014. SETTING: Atherosclerosis Risk in Communities Study (NC, MS, MD, MN). PARTICIPANTS: A total of 10,147 weighted hospitalizations for ADHF (64% female, 74% white, mean age 77 years), with ejection fraction ≥50%. MEASUREMENTS: ADHF classified by physician review, HFpEF defined by ejection fraction ≥50%. Body mass index (BMI) calculated from weight at hospital discharge. Obesity defined by BMI ≥30 kg/m2 , class III obesity by BMI ≥40 kg/m2 . RESULTS: When aggregated across 2005-2014, the mean BMI was higher for black compared to white patients (34 vs 30 kg/m2 ; P < .0001), as was prevalence of obesity (56% vs 43%; P < .0001) and class III obesity (24% vs 13%; P < .0001). Over time, the annual mean BMI and prevalence of class III obesity remained stable for black patients, but steadily increased for white patients, with annual rates statistically differing by race (P-interaction = .04 and P = .03, respectively). For both races, a U-shaped adjusted mortality risk was observed across BMI categories, with the highest risk among patients with a BMI ≥40 kg/m2 . CONCLUSION: Black patients were disproportionately burdened by obesity in this decade-long community surveillance of older hospitalized patients with HFpEF. However, temporal increases in mean BMI and class III obesity prevalence among white patients narrowed the racial difference in recent years. For both races, the worst survival was observed with class III obesity. Effective strategies are needed to manage obesity in patients with HFpEF.

Management of heart failure in cardiac amyloidosis using an ambulatory diuresis clinic.

BACKGROUND: Recurrent congestion in cardiac amyloidosis (CA) remains a management challenge, often requiring high dose diuretics and frequent hospitalizations. Innovative outpatient strategies are needed to effectively manage heart failure (HF) in patients with CA. Ambulatory diuresis has not been well studied in restrictive cardiomyopathy. Therefore, we aimed to examine the outcomes of an ambulatory diuresis clinic in the management of congestion related to CA. METHODS AND RESULTS: We retrospectively studied patients with CA seen in an outpatient HF disease management clinic for (1) safety outcomes of ambulatory intravenous (IV) diuresis and (2) health care utilization. Forty-four patients with CA were seen in the clinic a total of 203 times over 6 months. Oral diuretics were titrated at 96 (47%) visits. IV diuretics were administered at 56 (28%) visits to 17 patients. There were no episodes of severe acute kidney injury or symptomatic hypotension. There was a significant decrease in emergency department and inpatient visits and associated charges after index visit to the clinic. The proportion of days hospitalized per 1000 patient days of follow-up decreased as early as 30 days (147.3 vs 18.1/1000 patient days of follow-up, P< .001) and persisted through 180 days (33.6 vs 22.9/1000 patient days of follow-up, P< .001) pre- vs post-index visit to the clinic. CONCLUSIONS: We demonstrate the feasibility of ambulatory IV diuresis in patients with CA. Our findings also suggest that use of a HF disease management clinic may reduce acute care utilization in patients with CA. Leveraging multidisciplinary outpatient HF clinics may be an effective alternative to hospitalization in patients with HF due to CA, a population who otherwise carries a poor prognosis and contributes to high health care burden.

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.

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.

Racial disparities in the rate of cardiotoxicity of HER2-targeted therapies among women with early breast cancer.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-targeted therapies are highly effective at preventing breast cancer recurrence but are associated with cardiotoxicity in some patients, and minimal data are available regarding racial disparities in the incidence of this toxicity. The authors conducted a retrospective study to analyze the association of black or white race with treatment-induced cardiotoxicity and incomplete therapy among patients with HER2-positive early breast cancer. METHODS: Women with HER2-positive, stage I through III breast cancer who initiated (neo)adjuvant HER2-targeted therapy (trastuzumab with or without pertuzumab) from January 2005 to March 2015 at the authors' institution were eligible. We analyzed differences in the incidence of cardiotoxicity (a decline in the left ventricular ejection fraction to <50% AND an absolute drop in the left ventricular ejection fraction of ≥10% from baseline) and incomplete therapy (<52 weeks of HER2-targeted therapy) between black and white women in univariate and multivariable analyses. RESULTS: The authors identified 59 black patients and 157 white patients who had a median follow-up 5.2 years. The median patient age was 53 years and was similar for black and white patients. The 1-year cardiotoxicity incidence was 12% overall (95% confidence interval [CI], 7%-16%), 24% in black women (95% CI, 12%-34%), and 7% in white women (95% CI, 3%-11%). Black patients had a significantly greater probability of incomplete therapy compared with white patients (odds ratio, 4.61; 95% CI, 1.70-13.07; P = .002). High correlation was observed between a cardiotoxicity event and incomplete therapy (96% concordance). CONCLUSIONS: Black patients have a higher rate of cardiotoxicity and resultant incomplete adjuvant HER2-targeted therapy than white patients. This patient population may benefit from enhanced cardiac surveillance, cardioprotective strategies, and early referral to cardiology when appropriate. Cancer 2018;124:1904-11. © 2018 American Cancer Society.

Outcomes and worsening renal function in patients hospitalized with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) has been described as a disease of elderly subjects with female predominance and hypertension. Our clinical experience suggests patients with HFpEF from an urban population are far more heterogenous, with greater co-morbidities and significant inhospital morbidity. There are limited data on the hospitalization course and outcomes in acute decompensated HFpEF. Hospitalizations for acute heart failure at our institution from July 2011 to June 2012 were identified by International Classification of Diseases, Ninth Revision, codes and physician review for left ventricular ejection fraction ≥50% and were reviewed for patient characteristics and clinical outcomes. Worsening renal function (WRF) was defined as creatinine increase of ≥0.3 mg/dl by 72 hours after admission. Hospital readmission and mortality data were captured from electronic medical records and the Social Security Death Index. Of 434 heart failure admissions, 206 patients (47%) with HFpEF were identified. WRF developed in 40%, the highest reported in HFpEF to date, and was associated with higher blood pressure and lower volume of diuresis. Compared to previous reports, hospitalized patients with HFpEF were younger (mean age 63.2 ± 13.6 years), predominantly black (74%), and had more frequent and severe co-morbidities: hypertension (89%), diabetes (56%), and chronic kidney disease (55%). There were no significant differences in 1- and 12-month outcomes by gender, race, or WRF. In conclusion, we found hospitalized patients with HFpEF from an urban population develop a high rate of WRF are younger than previous cohorts, often black, and have greater co-morbidities than previously described.

Prediction of incident heart failure in general practice: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: A simple and effective heart failure (HF) risk score would facilitate the primary prevention and early diagnosis of HF in general practice. We examined the external validity of existing HF risk scores, optimized a 10-year HF risk function, and examined the incremental value of several biomarkers, including N-terminal pro-brain natriuretic peptide. METHODS AND RESULTS: During 15.5 years (210 102 person-years of follow-up), 1487 HF events were recorded among 13 555 members of the biethnic Atherosclerosis Risk in Communities (ARIC) Study cohort. The area under curve from the Framingham-published, Framingham-recalibrated, Health ABC HF recalibrated, and ARIC risk scores were 0.610, 0.762, 0.783, and 0.797, respectively. On addition of N-terminal pro-brain natriuretic peptide, the optimism-corrected area under curve of the ARIC HF risk score increased from 0.773 (95% CI, 0.753-0.787) to 0.805 (95% CI, 0.792-0.820). Inclusion of N-terminal pro-brain natriuretic peptide improved the overall classification of recalibrated Framingham, recalibrated Health ABC, and ARIC risk scores by 18%, 12%, and 13%, respectively. In contrast, cystatin C or high-sensitivity C-reactive protein did not add toward incremental risk prediction. CONCLUSIONS: The ARIC HF risk score is more parsimonious yet performs slightly better than the extant risk scores in predicting 10-year risk of incident HF. The inclusion of N-terminal pro-brain natriuretic peptide markedly improves HF risk prediction. A simplified risk score restricted to a patient's age, race, sex, and N-terminal pro-brain natriuretic peptide performs comparably to the full score (area under curve, 0.745) and is suitable for automated reporting from laboratory panels and electronic medical records.

Insurance and education predict long-term survival after orthotopic heart transplantation in the United States.

BACKGROUND: Insurance status and education are known to affect health outcomes. However, their importance in orthotopic heart transplantation (OHT) is unknown. The United Network for Organ Sharing (UNOS) database provides a large cohort of OHT recipients in which to evaluate the effect of insurance and education on survival. METHODS: UNOS data were retrospectively reviewed to identify adult primary OHT recipients (1997 to 2008). Patients were stratified by insurance at the time of transplantation (private/self-pay, Medicare, Medicaid, and other) and college education. All-cause mortality was examined using multivariable Cox proportional hazard regression incorporating 15 variables. Survival was modeled using the Kaplan-Meier method. RESULTS: Insurance for 20,676 patients was distributed as follows: private insurance/self-pay, 12,298 (59.5%); Medicare, 5,227 (25.3%); Medicaid, 2,320 (11.2%); and "other" insurance, 831 (4.0%). Educational levels were recorded for 15,735 patients (76.1% of cohort): 7,738 (49.2%) had a college degree. During 53 ± 41 months of follow-up, 6,125 patients (29.6%) died (6.7 deaths/100 patient-years). Survival differed by insurance and education. Medicare and Medicaid patients had 8.6% and 10.0% lower 10-year survival, respectively, than private/self-pay patients. College-educated patients had 7.0% higher 10-year survival. On multivariable analysis, college education decreased mortality risk by 11%. Medicare and Medicaid increased mortality risk by 18% and 33%, respectively (p ≤ 0.001). CONCLUSIONS: Our study examining insurance and education in a large cohort of OHT patients found that long-term mortality after OHT is higher in Medicare/Medicaid patients and in those without a college education. This study points to potential differences in the care of OHT patients based on education and insurance status.

Development of a quantitative donor risk index to predict short-term mortality in orthotopic heart transplantation.

BACKGROUND: No standard index based on donor factors exists for predicting mortality after orthotopic heart transplantation (OHT). We utilized United Network for Organ Sharing (UNOS) data to develop a quantitative donor risk score for OHT. METHODS: We examined a prospectively collected open cohort of 22,252 patients who underwent primary OHT (1996 to 2007). Of the 284 donor-specific variables, those associated with 1-year (year) mortality (exploratory p-value < 0.2) were incorporated into a multivariate (MV) logistic regression model. The final model contained donor factors that improved the explanatory power (by pseudo-R2, area under the curve and likelihood ratio test). A quantitative donor risk score was created using odds ratios (ORs) from the final model. For external validity, a cross-validation strategy was employed whereby the score was generated using a randomly generated subset of cases (n = 17,788) and then independently validated on the remaining patients (n = 4,464). RESULTS: A 15-point scoring system incorporated 4 variables: ischemic time; donor age; race mismatching; and blood urea nitrogen (BUN)/creatinine ratio. Derivation and validation cohort scores ranged from 1 to 15 and 1 to 12, respectively (mean 4.0 ± 2.1 for each). Each increase of 1 point increased the risk of 1-year death by 9% (OR = 0.09 [1.07 to 0.12]) in the derivation cohort and 13% (OR = 0.13 [1.08 to 0.18]) in the validation cohort (each p < 0.001). The odds of 1-year mortality by increments of 3 points were: 0 to 2 points (reference); 3 to 5 points (OR = 0.25 [1.12 to 0.40], p < 0.001); 6 to 8 pts (OR = 0.77 [1.56 to 2.02], p < 0.001); and 9 to 15 points (OR = 1.92 [1.54 to 2.39], p < 0.001). Donor risk score was predictive for 30-day mortality (OR = 0.11 [1.08 to 0.14], p < 0.001) and 5-year cumulative mortality (OR = 0.11 [1.09 to 0.13], p < 0.001). CONCLUSIONS: We present a novel donor risk index for OHT predicting short- and long-term mortality. This donor risk score may prove valuable for donor heart allocation and prognosis after OHT.

Impact of recipient body mass index on organ allocation and mortality in orthotopic heart transplantation.

BACKGROUND: It is unknown whether obesity affects organ allocation in orthotopic heart transplantation (OHT). The United Network for Organ Sharing (UNOS) database provides an opportunity to examine this issue. METHODS: We reviewed UNOS data to identify 27,002 OHT candidates placed on the heart transplantation wait list (1998 to 2007). Patients were stratified by body mass index (BMI) at listing. Multivariate Cox proportional hazards model estimated the chance of receiving OHT, adjusting for factors that might affect allocation. Mortality on the wait list and post-OHT mortality were estimated using the Kaplan-Meier method. RESULTS: Of 27,002 patients listed, the distribution of BMI was as follows: BMI 18.5 to 24.9, n = 9,734 (36.0%); BMI 25 to 29.9, n = 10,063 (37.2%); BMI 30 to 34.9, 5,500 (20.4%); and BMI > or =35, 1,705 (6.3%). BMI was strongly associated with a decrease in the likelihood of receiving OHT once on the wait list (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.95 to 0.96, p < 0.001). Patients with BMI > or =35 had a 46% lower likelihood of receiving a donor heart after risk adjustment (HR 0.54, 95% CI 0.49 to 0.60, p < 0.001). On the wait list, patients with extreme BMIs (> or =35) who were listed as UNOS Status 1 had the lowest cumulative survival (61% at 3 years). After OHT, patients with high BMI did not have increased short-term mortality at 30 days, 90 days or 1 year. CONCLUSIONS: Obese individuals wait longer and have a lower likelihood of receiving a donor heart after listing, despite similar short-term survival. The results of this study point to a potential provider bias for obese individuals in OHT.

Outcomes, health policy, and managed care: relationships between patient-reported outcome measures and clinical measures in outpatients with heart failure.

BACKGROUND: Patient-reported outcomes are increasingly used to assess the efficacy of new treatments. Understanding relationships between these and clinical measures can facilitate their interpretation. We examined associations between patient-reported measures of health-related quality of life and clinical indicators of disease severity in a large, heterogeneous sample of patients with heart failure. METHODS: Patient-reported measures, including the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQol Visual Analog Scale (VAS), and clinical measures, including peak VO(2), 6-minute walk distance, and New York Heart Association (NYHA) class, were assessed at baseline in 2331 patients with heart failure. We used general linear models to regress patient-reported measures on each clinical measure. Final models included for significant sociodemographic variables and 2-way interactions. RESULTS: The KCCQ was correlated with peak VO(2) (r = .21) and 6-minute walk distance (r = .27). The VAS was correlated with peak VO(2) (r = .09) and 6-minute walk distance (r = .11). Using the KCCQ as the response variable, a 1-SD difference in peak Vo(2) (4.7 mL/kg/min) was associated with a 2.86-point difference in the VAS (95% CI, 1.98-3.74) and a 4.75-point difference in the KCCQ (95% CI, 3.78-5.72). A 1-SD difference in 6-minute walk distance (105 m) was associated with a 2.78-point difference in the VAS (95% CI, 1.92-3.64) and a 5.92-point difference in the KCCQ (95% CI, 4.98-6.87); NYHA class III was associated with an 8.26-point lower VAS (95% CI, 6.59-9.93) and a 12.73-point lower KCCQ (95% CI, 10.92-14.53) than NYHA class II. CONCLUSIONS: These data may inform deliberations about how to best measure benefits of heart failure interventions, and they generally support the practice of considering a 5-point difference on the KCCQ and a 3-point difference on the VAS to be clinically meaningful.

Disparities in access to left ventricular assist device therapy.

BACKGROUND: Implantation of a left ventricular assist device (LVAD) has been shown to improve survival and quality of life among selected patients with end-stage heart failure. We hypothesized that utilization of this complex and expensive treatment modality would be influenced by disparities in access to health care. MATERIALS AND METHODS: We reviewed data from the National Inpatient Sample from 2002 to 2003. Patients were included in the study if they were admitted to the hospital with a primary diagnosis of congestive heart failure or cardiogenic shock. Patients older than 85 years of age and those with contraindications to LVAD therapy due to pre-existing medical conditions were excluded from the study. A multivariate logistic regression analysis was performed to determine the influence of patient characteristics (age, gender, race, comorbidities, socioeconomic status, insurance status, and population density of residence) as well as hospital characteristics (academic versus private and geographic region) on LVAD implantation. RESULTS: A total of 297,866 patients met the inclusion criteria for the study. Only 291 of these patients underwent LVAD implantation. Factors that adversely influenced access to therapy included age >65 (OR = 0.14), female gender (OR = 0.44), black race (OR = 0.29), admission to a non-academic center (OR = 0.16), and geographic region. CONCLUSIONS: LVAD implantation was significantly influenced by disparities in access to treatment. Systematic reform in the delivery of evolving medical technologies to patients is needed to eliminate these disparities.

Increased mortality at low-volume orthotopic heart transplantation centers: should current standards change?

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) mandate that orthotopic heart transplantation (OHT) centers perform 10 transplants per year to qualify for funding. We sought to determine whether this cutoff is meaningful and establish recommendations for optimal center volume using the United Network for Organ Sharing (UNOS) registry. METHODS: We reviewed UNOS data (years 1999 to 2006) identifying 14,401 first-time adult OHTs conducted at 143 centers. Stratification was by mean annual institution volume. Primary outcomes of 30-day and 1-year mortality were assessed by multivariable logistic regression (adjusted for comorbidities and risk factors for death). Sequential volume cutoffs were examined to determine if current CMS standards are optimal. Pseudo R2 and area under the receiver operating curve assessed goodness of fit. RESULTS: Mean annual volume ranged from 1 to 90. One-year mortality was 12.6% (n = 1,800). Increased center volume was associated with decreased 30-day mortality (p < 0.001). Decreased center volume was associated with increases in 30-day (odds ratio [OR] 1.03, 95% confidence interval [CI]: 1.02 to 1.03, p < 0.001) and 1-year mortality (OR 1.01, 95% CI: 1.01 to 1.02, p = 0.03--censored for 30-day death). The greatest mortality risk occurred at very low volume centers (

Transcriptomic biomarkers for individual risk assessment in new-onset heart failure.

BACKGROUND: Prediction of prognosis remains a major unmet need in new-onset heart failure (HF). Although several clinical tests are in use, none accurately distinguish between patients with poor versus excellent survival. We hypothesized that a transcriptomic signature, generated from a single endomyocardial biopsy, could serve as a novel prognostic biomarker in HF. METHODS AND RESULTS: Endomyocardial biopsy samples and clinical data were collected from all patients presenting with new-onset HF from 1997 to 2006. Among a total of 350 endomyocardial biopsy samples, 180 were identified as idiopathic dilated cardiomyopathy. Patients with phenotypic extremes in survival were selected: good prognosis (event-free survival for at least 5 years; n=25) and poor prognosis (events [death, requirement for left ventricular assist device, or cardiac transplant] within the first 2 years of presentation with HF symptoms; n=18). We used human U133 Plus 2.0 microarrays (Affymetrix) and analyzed the data with significance analysis of microarrays and prediction analysis of microarrays. We identified 46 overexpressed genes in patients with good versus poor prognosis, of which 45 genes were selected by prediction analysis of microarrays for prediction of prognosis in a train set (n=29) with subsequent validation in test sets (n=14 each). The biomarker performed with 74% sensitivity (95% CI 69% to 79%) and 90% specificity (95% CI 87% to 93%) after 50 random partitions. CONCLUSIONS: These findings suggest the potential of transcriptomic biomarkers to predict prognosis in patients with new-onset HF from a single endomyocardial biopsy sample. In addition, our findings offer potential novel therapeutic targets for HF and cardiomyopathy.

Value of clinician assessment of hemodynamics in advanced heart failure: the ESCAPE trial.

BACKGROUND: We determined whether estimated hemodynamics from history and physical examination (H&P) reflect invasive measurements and predict outcomes in advanced heart failure (HF). The role of the H&P in medical decision making has declined in favor of diagnostic tests, perhaps due to lack of evidence for utility. METHODS AND RESULTS: We compared H&P estimates of filling pressures and cardiac index with invasive measurements in 194 patients in the ESCAPE trial. H&P estimates were compared with 6-month outcomes in 388 patients enrolled in ESCAPE. Measured right atrial pressure (RAP) was <8 mm Hg in 82% of patients with RAP estimated from jugular veins as <8 mm Hg, and was >12 mm Hg in 70% of patients when estimated as >12 mm Hg. From the H&P, only estimated RAP > or =12 mm Hg (odds ratio [OR] 4.6; P<0.001) and orthopnea > or =2 pillows (OR 3.6; P<0.05) were associated with pulmonary capillary wedge pressure (PCWP) > or =30 mm Hg. Estimated cardiac index did not reliably reflect measured cardiac index (P=0.09), but "cold" versus "warm" profile was associated with lower median measured cardiac index (1.75 vs. 2.0 L/min/m(2); P=0.004). In Cox regression analysis, discharge "cold" or "wet" profile conveyed a 50% increased risk of death or rehospitalization. CONCLUSIONS: In advanced HF, the presence of orthopnea and elevated jugular venous pressure are useful to detect elevated PCWP, and a global assessment of inadequate perfusion ("cold" profile) is useful to detect reduced cardiac index. Hemodynamic profiles estimated from the discharge H&P identify patients at increased risk of early events.