Prognostic Value of the Physical Examination in Patients with Heart Failure and Atrial Fibrillation: Insights from the AF-CHF Trial

S34 Journal of Cardiac Failure Vol. 19 No. 8S August 2013 (Table). Absence of congestion was defined as the absence of jugular venous distension, dyspnea, rales, and pedal or sacral edema on hospital day 7 or discharge. The associations between Loop Dose, discharge congestion status, and all-cause mortality and worsening HF events (HF hospitalization; unscheduled outpatient or emergency department visit associated with IV therapy for HF; or death from HF) within 90 days of randomization were assessed. Results: Median Loop Dose for all subjects was 93 mg and did not differ in 2558 subjects with discharge congestion (89 mg) vs. 600 subjects without discharge congestion (107 mg), p50.36. At 90 days, mortality and worsening HF events occurred in 7.5% and 15.4% of subjects respectively. Higher Loop Dose was associated with clinical markers of more severe disease (Table) and increased risk of mortality (HR 1.37, p!0.001 for one unit increase in natural-log-transformed dose) and worsening HF (HR 1.68/2.35 as compared to Medium/Low Doses, p!0.001). The association between Loop Dose and outcome events did not differ in patients with or without persistent congestion at the time of hospital discharge (for all-cause mortality, with congestion HR 1.44 vs. without congestion HR 0.94, p50.10 for interaction term; and for worsening HF, with congestion HR 1.57 vs. without congestion HR 1.28, p50.18 for interaction term). Conclusion: Higher Loop Dose during hospitalization was associated with worse clinical status, increased short-term all-cause mortality, and increased risk of worsening HF events. The association between in-hospital diuretic dose and clinical outcomes did not differ in patients with or without clinical signs and symptoms of congestion at hospital discharge. Table 1. Average Daily Loop Diuretic Dose Low (560 mg) (n51006) LVEF (%) SEP (mmHg) NVHA class IV (%) BNP (pg/ml) eGFR (ml/min

29 123 36 535 60

Medium (61-120 mg) (n51063) 28 123 41 690 57

High (O120 mg) (n51145)

p-value

26 118 45

!001 !001 !001

925 52

!001 !001

095 Progression of Diastolic Dysfunction in Breast Cancer Patients after Chemotherapy Exposure Correlates with Advanced Age and Presence of Several Cardiovascular Risk Factors Wissam M. Abdallah1, Monica da Silva1, Darla Freehardt1, Brenda White1, Daniel J. Lenihan1, Douglas B. Sawyer1, Carrie Geisberg Lenneman1,2; 1Vanderbilt University Medical Center, Nashville, TN; 2University of Louisville, Louisville, KY Introduction: Chemotherapy-induced cardiotoxicity can occur acutely or chronically and manifest with systolic heart failure (HF) and/or heart failure with preserved ejection fraction (HFpEF). Left ventricular diastolic dysfunction (LVDD) after chemotherapy has been reported to occur as early as one hour and up to several months after anthracycline exposure. However, development of LVDD has not been shown to correlate with symptoms or progression to systolic HF. In patients exposed to potentially cardiotoxic chemotherapeutic agents, risk factors for developing LVDD, and potential progression to HFpEF, are not well-characterized. Furthermore, by considering diastolic dysfunction a form of structural heart disease, these patients may warrant re-classification as Stage B HF by ACC/AHA guidelines. Hypothesis: The aim of our study is to examine whether specific baseline cardiovascular risk factors (CVRF) and/or plasma neuregulin (NRG), a modulator of cardiac function, help predict which patients have progressive LVDD. Methods: Fifty-one patients newly diagnosed with breast cancer were prospectively enrolled prior to anthracycline and/or trastuzumab exposure. Baseline demographics and CVRF were collected. Plasma NRG and transthoracic echocardiograms (TTE) were obtained at baseline and 3 months after chemotherapy exposure. Patients with progressive LVDD were defined as those who developed LVDD from a normal diastolic filling pattern, transitioned to a higher stage of LVDD, or developed an indeterminate stage of LVDD (i.e. did not strictly satisfy the criteria for one particular diastolic dysfunction stage). Results: Of the 51 patients enrolled, 11 (21.6%) developed progressive LVDD. Patients with progressive LVDD were statistically older than those with no or unchanged LVDD (56.9 years vs. 49.3 years; p 5 0.009) and had a higher number of CVRF (3.2 vs. 2.0; p 5 0.01). The most prevalent CVRF were any history of tobacco use, hypertension, and hyperlipidemia. NRG levels, as well as LVEF, between both groups were unchanged at baseline and after 3 months of chemotherapy exposure. Patients with progressive LVDD were also more likely to be on a beta blocker (18.2% vs. 7.5%) or an ACE inhibitor (27.3% vs. 12.5%). Conclusions: Approximately one-fifth of breast cancer patients treated with potentially-cardiotoxic chemotherapy develop progressive LVDD. Advanced age and the presence of multiple CVRF, namely tobacco exposure, hypertension, and hyperlipidemia, increases the risk of developing progressive LVDD. The higher usage of beta blocker and ACE inhibitor therapy in patients with progressive LVDD is likely due to underlying hypertension. Patients with progressive LVDD may qualify for Stage B HF and hence require more aggressive risk factor modification as well as initiation and optimization of heart failure therapy.

096 Prognostic Value of the Physical Examination in Patients with Heart Failure and Atrial Fibrillation: Insights from the AF-CHF Trial Guillem Caldentey1, Paul Khairy1, Denis Roy1, Hugues Leduc2, Mario Talajic1, Normand Racine1, Michel White1, Eileen O’Meara1, Jean L. Rouleau1, Anique Ducharme1; 1Montreal Heart Institute, Montreal, QC, Canada; 2Montreal Heart Institute Coordinating Center, Montreal, QC, Canada Objectives: We sought to assess the prognostic value of physical examination in a modern treated heart failure population. Background: The physical examination is the cornerstone of the evaluation and monitoring of patients with heart failure. Yet, the prognostic value of congestive signs, i.e., peripheral edema, jugular venous distension, a third heart sound, and pulmonary rales, has not been assessed in the current era. Methods: A post hoc analysis was conducted on all 1376 patients, 81% male, mean age 67611 years, with symptomatic left ventricular systolic dysfunction enrolled in the atrial fibrillation and congestive heart failure (AF-CHF) trial. The prognostic value of baseline physical examination findings was assessed in univariate and multivariate Cox regression analyses. Results: Peripheral edema was observed in 425 (30.9%), jugular venous distension in 297 (21.6%), a third heart sound in 207 (15.0%), and pulmonary rales in 178 (12.9%) patients. Death from cardiovascular causes occurred in 357 (25.9%) patients over a mean follow-up of 37619 months. All four physical examination findings were associated with cardiovascular mortality in univariate analyses (all P-values !0.01). In multivariate analyses, taking all four signs as potential covariates, only rales [hazard ratio 1.41, 95% confidence interval (1.07, 1.86), P50.013] and peripheral edema [HR 1.25, 95% CI (1.00, 1.57), P50.048] were associated with cardiovascular mortality, independent of other variables. Conclusion: In the modern era, the physical examination, particularly pulmonary rales and peripheral edema, continue to provide important prognostic information in patients with congestive heart failure, independent of clinical variables and medical therapy.

097 Digoxin May Increase the Risk of 30-Day All-Cause Hospital Admission in Ambulatory Older Patients with Chronic Heart Failure and Preserved Ejection Fraction Taimoor Hashim1, Gregg C. Fonorow2, Shereen Elbaz1, Charity Morgan1, Kanan Patel1, Jose A. Tallaj1,3, Salpy V. Pamboukian1, Robert C. Bourge1, Ali Ahmed1,3; 1 University of Alabama at Birmingham, Birmingham, AL; 2University of California Los Angeles, Los Angeles, CA; 3Veterans Affairs Medical Center, Birmingham, AL Background: Heart failure (HF) is the leading cause for hospital readmission for Medicare beneficiaries. Under the new US healthcare reform law hospitals face financial penalties for excessive 30-day all-cause readmissions. Digoxin reduces 30-day all-cause hospitalization in older patients with HF and reduced ejection fraction (HFrEF). The aim of the current study was to examine the above effect of digoxin in older patients with HF and preserved EF (HFpEF). Methods: In the randomized placebo-controlled Digitalis Investigation Group (DIG) ancillary study, 988 patients had HFpEF (EF O45%), of whom 631 were $65 years

Fig. 1. Kaplan Meier.