Use of Biomarkers to Predict Readmission for Congestive Heart Failure.

Acute decompensated heart failure (ADHF) is a major reason for repeated hospitalizations. Identifying those patients with ADHF at risk for readmission is critical so that preventive interventions can be implemented. Biomarkers such as B-type natriuretic peptide (BNP), high-sensitivity troponin I, and galectin-3 (Gal-3) assessed at discharge may be useful, although their role in predicting short-term readmission is not well defined in the literature. We enrolled and had follow-up data for 101 participants admitted to our facility from April 2013 to March 2015 with a primary diagnosis of ADHF. Gal-3, high-sensitivity troponin I, and BNP were obtained within 48 hours before hospital discharge after management of ADHF. Gal-3 was assessed using 2 commercially available assays. We compared subjects who were and were not readmitted. Discharge BNP was found to be a significant predictor of 30- and 60-day readmission (area under the curve [AUC] 0.69 [p = 0.046], AUC 0.7 [p = 0.005], respectively). The addition of Gal-3 to discharge BNP provided significantly improved prediction of 60-day readmission. Gal-3 alone was found to be a significant predictor of 60-day readmission in patients with preserved ejection fraction (AUC 0.85, p <0.001). The net reclassification improvement was 55.2 (p = 0.037). Using multivariate analysis, for every 100 pg/L BNP increase, the probability of readmission increased by approximately 10%, and for every 1-ng/ml Gal-3 increase, the probability further increased 8%. A statistically significant net reclassification improvement was not found on examination of 30-day readmission. In conclusion, measurement of both Gal-3 and BNP at hospital discharge provides significant prediction of hospital readmission within 60 days. When combined, the prediction of readmission is significantly improved.

Short- and Long-term Biologic Variability of Galectin-3 and Other Cardiac Biomarkers in Patients with Stable Heart Failure and Healthy Adults.

BACKGROUND: Galectin-3 (Gal-3) has been suggested as a prognostic biomarker in heart failure (HF) patients that may better reflect disease progression than traditional markers, including B-type natriuretic peptide (BNP) and cardiac troponins. To fully establish the utility of any biomarker in HF, its biologic variability must be characterized. METHODS: To assess biologic variability, 59 patients were prospectively recruited, including 23 male and 16 female patients with stable HF and 10 male and 10 female healthy individuals. Gal-3, BNP, and high-sensitivity cardiac troponin I (hs-cTnI) were assayed at 5 time points within a 3-week period to assess short-term biologic variability. Long-term (3-month) biologic variability was assessed with samples collected at enrollment and after 4, 8, and 12 weeks. RESULTS: Among healthy individuals, mean short-term biologic variability, expressed as intraindividual CV (CVI), was 4.5% for Gal-3, 29.0% for BNP, and 14.5% for hs-cTnI; long-term biologic variability was 5.5% for Gal-3, 34.7% for BNP, and 14.7% for hs-cTnI. In stable HF patients, mean short-term biologic variability was 7.1% for Gal-3, 22.5% for BNP, and 8.5% for hs-cTnI, and mean long-term biologic variability was 7.7% for Gal-3, 27.6% for BNP, and 9.6% for hs-cTnI. CONCLUSIONS: The finding that Gal-3 has minimal intraindividual biological variability adds to its potential as a useful biomarker in HF patients.

Impact on Patient Management and Outcome of Switching between 2 Contemporary Sensitive Cardiac Troponin Assays.

BACKGROUND: Myocardial infarction is characterized by an increase of cardiac troponin I (cTnI) above the 99th percentile of a reference population. Our hospital switched from 1 contemporary cTnI assay to another and observed a doubling of cTnI results above the assays' respective 99th percentile cutoffs. We investigated the potential impact on inpatient management and outcomes. METHODS: We performed a retrospective cohort study of 45 498 individuals with ≥1 cTnI result between January 2013 and June 2014. The Dimension cTnI assay was used in 2013; the Abbott Architect cTnI assay was used in 2014. RESULTS: Before switching cTnI assays, 19.2% (4742/30 872) of patients had at least 1 of the first 3 cTnIs above the 99th percentile (0.07 µg/L). After switching to the Architect cTnI assay, 31.4% (4034/14 626) of patients had at least 1 cTnI above the 99th percentile (0.03 µg/L). This increase was due to the difference in the assays' 99th percentile cutoffs. Having an increased cTnI reported on the Architect assay that would not have been reported as such on the Dimension assay (0.03-0.06 µg/L) correlated with increased inpatient mortality, length of stay, non-ST elevation myocardial infarction diagnosis, therapeutic heparin use, and percutaneous coronary intervention, relative to individuals with cTnI <0.03 µg/L. CONCLUSIONS: The changes observed in patient outcomes and management were likely due to the increased sensitivity and lower 99th percentile cutoff of the Architect assay. It is important to recognize the potential impact that differences in sensitivity and assay configuration may have on patient management.

Graft survival after cardiac transplantation for alcohol cardiomyopathy.

BACKGROUND: Alcohol cardiomyopathy (ACM) constitutes up to 40% of patients with non-ischemic dilated cardiomyopathy. Transplant-free survival is worse for patients with ACM versus idiopathic dilated cardiomyopathy (IDCM) with continued exposure. The prognosis for patients with ACM after cardiac transplantation is unknown. METHODS: We evaluated adults who underwent single-organ, cardiac transplantation from 1994 to 2009 with a diagnosis of ACM (n=134) or IDCM (n=10,243) in the Organ Procurement Transplantation Network registry. Kaplan-Meier curves were generated by cohort for time until graft failure, cardiac allograft vasculopathy, and hospitalization for rejection. A Cox proportional hazards model was created to determine factors associated with each outcome. RESULTS: Patients with ACM were more likely to be males (P<0.0001), minorities (P<0.0001), and smokers (P=0.0310) compared with IDCM. Overall graft survival was lower for the ACM cohort (P=0.0001). After multivariate analysis, ACM was not independently associated with graft survival (HR 1.341, 95% CI 0.944-1.906, P=0.1017). Creatinine, total bilirubin, minority ethnicity, graft under-sizing, life support, diabetes, and donor age were independent predictors of graft failure. There were no significant differences between primary cause of death, vasculopathy, or rejection. CONCLUSIONS: There was no association between ACM and graft survival in this large registry study, but poorer overall survival in the ACM cohort was associated with other recipient characteristics.

Executive dysfunction and depressive symptoms associated with reduced participation of people with severe congestive heart failure.

OBJECTIVE: We investigated participation levels and relationships among cognition, depression, and participation for people with severe congestive heart failure (CHF). METHOD: People with severe CHF (New York Heart Association Class III or IV) awaiting heart transplantation (N = 27) completed standardized tests of cognition and self-report measures of executive dysfunction, depressive symptoms, and participation. RESULTS: Possible depression (64%) and cognitive impairment (15%-59%) were prevalent. Participants reported significant reductions in participation across all activity domains since CHF diagnosis (ps < .001). Worse executive dysfunction and depressive symptoms were associated with reduced participation and together accounted for 35%-46% of the variance in participation (ps < .01). CONCLUSION: Participation restrictions associated with CHF are not limited to physically demanding activities and are significantly associated with executive dysfunction and depression. Cardiac rehabilitation should address cognitive and psychological functioning in the context of all life situations instead of focusing solely on physical function and disability.

Acute decompensated heart failure: contemporary medical management.

Hospitalizations for acute decompensated heart failure are increasing in the United States. Moreover, the prevalence of heart failure is increasing consequent to an increased number of older individuals, as well as to improvement in therapies for coronary artery disease and sudden cardiac death that have enabled patients to live longer with cardiovascular disease. The main treatment goals in the hospitalized patient with heart failure are to restore euvolemia and to minimize adverse events. Common in-hospital treatments include intravenous diuretics, vasodilators, and inotropic agents. Novel pharmaceutical agents have shown promise in the treatment of acute decompensated heart failure and may simplify the treatment and reduce the morbidity associated with the disease. This review summarizes the contemporary management of patients with acute decompensated heart failure.

Should UNOS Status 2 patients undergo transplantation?

BACKGROUND: With recent improvements in medical and device therapy, the benefit of cardiac transplantation for UNOS Status 2 patients has been questioned. No randomized trial has been performed to compare transplantation versus contemporary medical therapy. METHODS: Between January 1996 and December 2003, 203 patients were listed at our institution for heart transplantation as UNOS Status 2. We performed a retrospective review to determine outcomes in these patients. RESULTS: Demographics of this cohort revealed a mean age of 52 years, female sex in 28%, and ischemic etiology in 47%. Eighty-one patients (40%) had an implantable cardiac defibrillator. A total of 64 patients (32%) had to be upgraded in their UNOS status, with 9 requiring a left ventricular assist device. Of the entire group, 95 (47%) underwent transplantation at a mean time of 303 days, 45 (22%) died while waiting at a mean time of 397 days, and 24 (12%) were removed from the waiting list due to deterioration in medical condition such that transplantation was no longer an option. The remaining patients continue to wait or have been removed from consideration due to improved condition. Survival at 1- and 3-years postlisting was 94% and 87% for patients who received transplants compared to 81% and 57% for patients who did not receive transplants (P < .01). CONCLUSION: A significant number of patients listed as Status 2 are upgraded in UNOS status or die while on the waiting list. Early and midterm survival is significantly better with transplantation. Identification of variables associated with deterioration may allow for better risk stratification in the future. At this point, transplantation offers the best outcome.

Prospective comparison of ventilatory equivalent versus peak oxygen consumption in predicting outcomes of patients with heart failure.

In patients with heart failure (HF), peak exercise oxygen consumption (VO2) is an important prognostic tool on which critical clinical decisions are made. However, recent retrospective data have suggested that ventilatory equivalent (VE = ventilation [liters per minute]/VO2 [liters per minute]) may be a stronger predictor of outcomes than VO2 in patients with HF on modern medical therapies. We prospectively collected baseline demographics, cardiovascular history, hemodynamics, and exercise ventilatory data from 221 consecutive patients with HF who underwent treadmill exercise VO2 testing. The composite primary end point was death or heart transplantation. Mean follow-up was 508 days, during which 27 events occurred (13 deaths and 14 transplantations). One-year event-free survival was 88% (n = 104 with 1-year follow-up). Mean age was 49 years, 68% were men, 84% were taking beta blockers, 82% were taking angiotensin-converting enzyme inhibitors, and 21% had an implantable cardioverter-defibrillator. Mean VO2 was 16 +/- 5 ml/kg/min. Mean VE was 47.4 +/- 15.2. Univariate predictors of events included lower VO2 (p <0.0001), higher heart rate at rest (p = 0.05), and presence of an implantable cardioverter-defibrillator (p = 0.024). Higher VE (p = 0.10) and lower maximum systolic blood pressure (p = 0.09) were of borderline significance. Age, gender, HF etiology or severity, and other ventilatory parameters were not significant predictors. Multivariate models that incorporated VE, VO2, or their combination confirmed VO2 as an independent predictor of event-free survival (p < or =0.0002); VE did not independently predict outcomes. Other independent predictors were higher heart rate at rest (p < or =0.02) and presence of an implantable cardioverter-defibrillator (p < or =0.04). In conclusion, peak VO2, but not VE, predicts clinical outcomes of patients with HF who are treated with contemporary medical therapies.

Alcohol consumption and prognosis in patients with left ventricular systolic dysfunction after a myocardial infarction.

OBJECTIVES: We assessed the influence of alcohol intake on the development of symptomatic heart failure (HF) in patients with left ventricular (LV) dysfunction after a myocardial infarction (MI). BACKGROUND: In contrast to protection from coronary heart disease, alcohol consumption has been linked to cardiodepressant effects and has been considered contraindicated in patients with HF. METHODS: The Survival And Ventricular Enlargement (SAVE) trial randomized 2231 patients with a LV ejection fraction (EF) <40% following MI to an angiotensin-converting enzyme inhibitor or placebo. Patients were classified as nondrinkers, light-to-moderate drinkers (1 to 10 drinks/week), or heavy drinkers (>10 drinks/week) based on alcohol consumption reported at baseline. The primary outcome was hospitalization for HF or need for an open-label angiotensin-converting enzyme inhibitor. Analyses were repeated using alcohol consumption reported three months after MI. RESULTS: Nondrinkers were older and had more comorbidities than light-to-moderate and heavy drinkers. In univariate analyses, baseline light-to-moderate alcohol intake was associated with a lower incidence of HF compared with nondrinkers (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.57 to 0.87), whereas heavy drinking was not (HR 0.91; 95% CI 0.67 to 1.23). After adjustment for baseline differences, light-to-moderate baseline alcohol consumption no longer significantly influenced the development of HF (light-to-moderate drinkers HR 0.93; 95% CI 0.75 to 1.17; heavy drinkers HR 1.25; 95% CI 0.91 to 1.72). Alcohol consumption reported three months after the MI similarly did not modify the risk of adverse outcome. CONCLUSIONS: In patients with LV dysfunction after an MI, light-to-moderate alcohol intake either at baseline or following MI did not alter the risk for the development of HF requiring hospitalization or an open-label angiotensin-converting enzyme inhibitor.

Effect of antecedent systemic hypertension on subsequent left ventricular dilation after acute myocardial infarction (from the Survival and Ventricular Enlargement trial).

Whether antecedent systemic hypertension influences the risk of subsequent left ventricular (LV) dilation in patients after an acute myocardial infarction with LV systolic dysfunction is unclear. We assessed echocardiographic evidence of ventricular remodeling from baseline (mean +/- SD 11 +/- 3 days) to 2 years after an acute myocardial infarction in 122 hypertensive (defined as a history of treated hypertension, baseline systolic blood pressure > or =140 or baseline diastolic blood pressure > or =90 mm Hg) and 334 nonhypertensive patients in the Survival and Ventricular Enlargement echocardiographic substudy. Compared with nonhypertensives, baseline heart size, defined as the sum of the average short- and long-axis LV cavity areas, was similar (70.1 +/- 11.9 vs 68.8 +/- 11.2 cm(2), p = 0.33 at end-diastole; 50.1 +/- 11.3 vs 48.8 +/- 10.8 cm(2), p = 0.31 at end-systole), but short-axis LV myocardial area (24.7 +/- 4.3 vs 25.7 +/- 5.0 cm(2), p = 0.043) and wall thickness (1.15 +/- 0.16 vs 1.21 +/- 0.17 cm, p = 0.004) at end-diastole were greater among hypertensives. The myocardial infarct segment lengths were similar in the 2 groups (p = 0.22). Although LV cavity areas increased significantly in the 2 groups from baseline to 2 years (p < or =0.001), the increase was significantly greater in hypertensives than in nonhypertensives (+5.6 +/- 11.5 vs +2.2 +/- 10.7 cm(2), p = 0.005 at end-diastole; +6.23 +/- 12.75 vs +2.94 +/- 11.4 cm(2), p = 0.012 at end-systole). There was no concomitant difference in the change in LV myocardial area or LV wall thickness between the 2 groups (p >0.30). After adjusting for known confounders, antecedent hypertension was associated with a doubling of the risk of LV dilation (50.8% vs 37.7%, odds ratio 2.09, 95% confidence interval 1.27 to 3.45, p = 0.004). This association was not modified by diabetes mellitus, myocardial infarct segment length, or captopril use (all p values for interaction >0.10). We conclude that antecedent hypertension is associated with subsequent LV dilation in patients after acute myocardial infarction with LV systolic dysfunction.

Survival of patients removed from the heart transplant waiting list.

OBJECTIVE: End-stage heart failure has been associated with high mortality in the absence of transplantation. We evaluated the outcome of patients receiving optimal medical therapy who were removed from the cardiac transplant waiting list to determine survival and predictors of mortality. METHODS: We performed a retrospective review of 27 patients removed from the cardiac transplant waiting list from 1999 to 2001 at our institution. RESULTS: Mean age was 53 +/- 11 years; 16 of the patients were male. Status was IB in 3 cases and II in 24. Median time on the list was 32 months, and median follow-up was 2.9 years. Patients were removed from the transplant list because of either clinical improvement (group A, n = 18) or deterioration (group B, n = 9). In group A, 13 patients had improved functional status and 10 were in New York Heart Association class 1 or 2; 16 had improved echocardiographic left ventricular function. Survivals at 3 years were 100% in group A and 44% in group B (P <.01). CONCLUSION: Patients with end-stage heart failure who have clinical response to medical therapy have excellent 3-year survival. These data suggest the necessity of close evaluation of patients waiting for transplantation, with a low threshold for inactivation if persistent clinical improvement is observed.

Timing of cardiac transplantation in patients with heart failure receiving beta-adrenergic blockers.

BACKGROUND: Previous work shows that patients with heart failure patients who have peak oxygen consumption (VO2 peak) >14 ml/kg/min do not derive a survival benefit from cardiac transplantation. However, this was shown before beta-blocker therapy for patients with systolic heart failure became common, and beta-blockers improve survival in patients with heart failure without changing VO(2) peak. Our purpose was to re-evaluate the utility of VO(2) peak >14 ml/kg/min as an indicator of the need for cardiac transplantation in patients with heart failure who are taking beta-blockers. METHODS: Actuarial, hemodynamic, and exercise ventilatory data were collected from 540 patients with heart failure, 256 of whom were taking beta-blockers. We tracked death and cardiac transplantation. We stratified the percentage of patients event-free 1 and 3 years after VO(2) peak study by their VO(2) peak and beta-blocker status, and compared 1- and 3-year post-transplant survival (United Network of Organ Sharing [UNOS] data). We also compared total mortality for the patients with heart failure as stratified by beta-blocker stats and VO(2) peak (excluding the 42 who underwent transplantation) with UNOS post-transplant survival. RESULTS: Patients with heart failure who were receiving beta-blockers and whose VO(2) peak was > or =12 ml/kg/min had greater 1- and 3-year event-free survival rates (95% confidence intervals, 92.6%-96.6% and 85.8%-96.0%) than did post-transplant patients (83.9%-86.3% and 75.4%-76.6%). However, in patients with heart failure not taking beta-blockers, VO(2) peak <14 ml/kg/min was associated with worse 3-year survival (38.9 - 62.1%) than that for post-transplant patients. Excluding the 42 patients with heart failure in our study who underwent transplantation and then evaluating survival of the remaining patients with heart failure (not event-free survival) did not substantially change these results. CONCLUSIONS: Patients with heart failure who are receiving beta-blockers do not derive a survival advantage at 1 and 3 years after cardiac transplantation if VO(2) peak is > or =12 ml/kg/min. Patients not taking beta-blockers whose VO(2) peak is <14 ml/kg/min have superior survival with cardiac transplantation.

The effect of beta-adrenergic blockers on the prognostic value of peak exercise oxygen uptake in patients with heart failure.

OBJECTIVES: Our aim was to determine the effect of beta-adrenergic blockade on the prognostic value of peak oxygen consumption testing in patients with heart failure. BACKGROUND: Peak oxygen consumption has been shown to be a useful prognostic tool in patients with heart failure. However, studies demonstrating the utility of peak oxygen consumption were conducted before beta-blocker therapy became widespread. Thus, our objective was to determine the effect of beta-blockers on the prognostic value of peak oxygen consumption in patients with heart failure. METHODS: Actuarial, anthropomorphic, hemodynamic and exercise ventilatory data were collected from 369 patients with heart failure. Death and orthotopic heart transplants were the events tracked. Patients were divided into those taking beta-blockers and those not taking them. Event-free survival days were calculated. RESULTS: One hundred ninety-nine patients on beta-blockers and 170 not on beta-blockers were studied. There were 40 orthotopic heart transplants and 82 deaths during follow-up. Peak oxygen consumption (milliliters per kilogram per minute) trended toward being an independent predictor of event-free survival (p = 0.055). In patients on and not on beta-blockers, a peak oxygen consumption of >14 ml/kg.min was associated with a 1-year event rate of approximately half of that associated with a peak oxygen consumption