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Early Therapy with Nesiritide in Hospitalized Patients with Acute Decompensated Heart Failure Associated with Reduced Costs: A Markov Analysis
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Journal of Cardiac Failure Vol. 11 No. 6 Suppl. 2005
330
332
Fatal Myocardial Rupture after Acute MI Complicated by HF or LVSD: The VALIANT Trial F. Shamshad1, S. Kenchaiah2, P. V. Finn2, J. Soler-Soler3, L. Kober4, Y. Belenkov5, S. Varshavsky6, S. D. Solomon1; 1Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA; 2Division of Aging, Brigham and Women’s Hospital, Boston, MA; 3Servei de Cardiologia, Hospital General Universitari Vall d’Hebron, Barcelona, Spain; 4Department of Cardiology, Rigshospitalet, Copenhagen, Denmark; 5 Cardiology Research Institute, Moscow, Russian Federation; 6Evidence Clinical and Pharmaceutical Research, Los Altos, CA
Early Therapy with Nesiritide in Hospitalized Patients with Acute Decompensated Heart Failure Associated with Reduced Costs: A Markov Analysis Juan Blackburn1, Robert J. DiDomenico1, Daniel E. Hilleman2, Surrey M. Walton1, Glen T. Schumock1; 1Center for Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL; 2Medicine and Pharmacy Practice, Creighton University, Omaha, NE
Purpose: Cardiac rupture is a devastating complication of myocardial infarction (MI). We sought to identify risk factors for cardiac rupture in the first 30 days following high-risk MI. Methods: The VALsartan In Acute myocardial iNfarcTion (VALIANT) trial compared valsartan, captopril, or both in 14,703 high-risk patients post-MI. Cardiac rupture was identified in 45 (0.31%) patients (33 by autopsy, 8 by echo, 4 by surgical procedure), occurred 3 to 12 days (mean 9.8 ⫾ 6) after qualifying MI (free wall 82%, interventricular septum 11%, both 7%), and accounted for 7.6% (45/ 589) of deaths in the first 30 days. Results: Compared with the rest of the VALIANT cohort (n ⫽ 14,658), cardiac rupture was associated with older age, female sex, hypertension, Killip class ⱖ2, inferior wall MI, Q-wave MI, thrombolytic therapy, and heparin use (all P values ⬍0.05). Peak creatine kinase levels were similar in the 2 groups (11.0 ⫾ 7.8 vs. 10.0 ⫾ 6.0; P ⫽ 0.53). In age- and sex-adjusted analyses, Killip class ⱖ2, inferior wall MI, Q-wave MI, and concomitant use of heparin were associated with an increased risk of cardiac rupture. Rupture accounted for 24% of all autopsy proven deaths (n ⫽ 138) in the first 30 days. Conclusions: Our data suggest that higher Killip class, Q-wave MI, inferior MI, and heparin use are risk factors for cardiac rupture post-MI, in patients with heart failure or left ventricular systolic dysfunction. Incomplete ascertainment may result in an underestimate of the true incidence of rupture.
Age, yrs, mean ⫾ Female, % Hypertension Killip class ⱖ2, % Inferior wall MI Q-wave MI Heparin use
Rupture (n ⫽ 45)
Non-rupture (n ⫽ 14,658)
OR (95% CI)
P value
70.3 ⫾ 8.1 46.7 71.1 88.9 53.5 88.6 68.9
64.8 ⫾ 11.8 31.0 55.0 71.9 34.3 66.5 51.6
1.70 (0.88–3.27) 2.65 (1.04–6.76) 2.21 (1.21–4.03) 4.95 (1.94–12.66) 2.07 (1.10–3.90)
0.11 0.041 0.010 ⬍0.001 0.024
Introduction: Heart failure (HF) is a common clinical syndrome associated with morbidity, mortality, and a significant economic burden to patients, providers, and society. Acute decompensated heart failure (ADHF) leads to frequent hospital admissions, which account for up to 70% of the cost of HF. Nesiritide, a recombinant form of human b-type natriuretic peptide, may reduce downstream resource utilization and improve patient outcomes when used early in the treatment course. Hypothesis: The purpose of this study was to evaluate the costs and patient outcomes of nesiritide, given within 24 hours of hospitalization, versus standard therapy for the treatment of ADHF. Methods: A Markov model of ADHF was developed using TreeAge Pro Healthcare software (TreeAge Inc., Williamstown, MA). The model incorporates complications of therapy (atrial fibrillation and renal failure), location of inpatient care (intensive care unit, inpatient ward, or emergency department only), and hospital readmissions. Three stages of disease were included within each cycle of the model: well (survive ADHF hospitalization without suffering ADHF readmission), sick (survive ADHF hospitalization but suffer ADHF readmission), and death. Transition probabilities were calculated from previous published clinical trials. Estimates of hospital costs were obtained from a pilot study conducted at Creighton University Medical Center. The model was run over 6 cycles of one month each. The analysis was conducted from the hospital perspective. Results: Over 6 months, the total hospital costs (including all readmissions) for a patient treated with nesiritide or standard therapy were $9,787.65 and $10,914.28, respectively (2004 US dollars), a net decrease of $1,126.63 favoring nesiritide. Cost differences were largely attributable to a lower probability of readmission for patients receiving nesiritide. Survival at 6 months also favored nesiritide, with net gain of 0.081 years per patient over standard therapy. Conclusions: Our model predicts that nesiritide, given within 24 hours of hospitalization for ADHF, reduces overall costs and may improve survival over 6 months compared to standard therapy.
331
333
The Effect of Glycemic Control on Heart Failure Severity in Diabetics Geetha Bhat1,2, Jeff Stidam1, Margaret Dugan2, Kay Padgett2; 1Division of Cardiology, University of Louisville, Louisville, KY; 2Heart Failure & Cardiac Transplant Center, Jewish Hospital, Louisville, KY
Additive Effect of Increased Urea and Creatinine Levels Detected during Admission for Acute Decompensated Heart Failure in Relation to Long-Term Prognosis Stella M. Macin1, Juan P. Cimbaro Canella1, Eduardo R. Perna1, Valeria Franciosi1, Ariel Szyszko1, Jorge O. Kriskovich1, Augusto P. Bayol1, Walter Vargas Morales1, Bilda Gonzalez Arjol2; 1Heart Failure Clinic, Instituto de Cardiologia J. F. Cabral, Corrientes, Argentina; 2Laboratory, Instituto de Cardiologia J. F. Cabral, Corrientes, Argentina
Introduction: Glycosylated hemoglobin (Hb A1c) is an index of metabolic control in diabetes (D). Recent studies suggest that poor glycemic control in diabetic patients (pts) indicated by elevated Hb A1c levels may be associated with increased risk of heart failure (HF). Our goal was to investigate the association between Hb A1c level and severity of HF in advanced HF pts with D. Methods: Among 250 pts referred for cardiac transplantation, 71 consecutive pts with advanced HF and D underwent evaluation with blood glucose, serum creatinine, Hb A1c, BNP, cardiopulmonary exercise testing and right heart catheterizaton. Pts were divided into two groups based on Hb A1c ⱕ 6.5% (Group A, mean Hb A1c 5.6 ⫾ 0.7) and Hb A1c ⬎6.5% (Group B, mean Hb A1c 8.6 ⫾ 1.9). Results: Parameter (mean value) Age (years) Gender (male %) Peak oxygen consumption (V02) ml/kg/minute BNP (pg/ml) Pulmonary capillary wedge (PCW) pressure (mm Hg) Serum glucose (mg/dl) Creatinine BMI (kg/m2) % on Insulin
Hb A1c ⱕ 6.5% (Group A: n ⫽ 29)
Hb A1c ⬎ 6.5% (Group B: n ⫽ 42)
52.7 ⫾ 12.3 76 17.0 ⫾ 1.5
52.6 ⫾ 11.2 79 14.7 ⫾ 2.9
0.98 0.97 0.06
312.0 ⫾ 232.7 19.7 ⫾ 7.9
577.3 ⫾ 483.6 24.3 ⫾ 8.3
0.01* 0.06
124 ⫾ 59 1.4 ⫾ 0.5 27.9 ⫾ 8.0 35.7
201 ⫾ 100 1.3 ⫾ 0.4 29.8 ⫾ 6.2 71.4
0.001* 0.61 0.30 0.01*
P value
*p ⱕ 0.05 Conclusion: BNP was significantly elevated in diabetic pts with Hb A1c ⬎ 6.5%. In Group B there was a trend towards increased severity of symptoms and hemodynamics demonstrated by lower peak VO2 and higher PCW pressure. Significantly higher percentage of pts with elevated Hb A1c (group B) were on insulin compared to group A. Poor glycemic control in HF pts appears to have negative impact on functional capacity and severity of symptoms. Persistent glucose intolerance as shown by elevated Hb A1c ⬎ 6.5% may be contributing to increased fluid retention reflected by worse PCW pressure and significantly higher BNP in group B. Tight control of hyperglycemia may improve prognosis in diabetic pts with HF. The effect of improved glycemic control on clinical outcomes such as frequency of hospitalization and survival in advanced HF pts with D deserves further study.
Objective: To evaluate the prognostic role of early combined detection of elevated levels of urea and creatinine in patients hospitalized with decompensated heart failure (DHF) on the long-term outcome. Material and Methods: Two hundred and fortyone consecutive patients were included because of DHF, between nov/2002-nov/2003. At the time of admission the urea and creatinine cutoff value were selected using the ROC curve in order to detect combined events (death and rehospitalization due to DHF). Renal dysfunction (RD) was defined as a urea and/or creatinine level above the cutoff value. Results: The mean age was 65.4 ⫾ 11.6 years, 64% were male, and 42.3% had an ischemic etiology. During follow up, the incidence of events was 44.4% (107 patients). The area under the ROC curve to predicting events for urea and creatinine was 0.59 y 0.57, respectively. The cut-off, sensitivity and specificity were: urea 0.55 mg/dl, 57% and 63%, respectively; creatinine 1.17 mg/dl, 58% y 62%, respectively. During admission 144 (60.4%) patients showed renal deterioration, from which 82 patients (57%) had elevated both markers, 29 (20.1%) had only increased levels of creatinine, and 33 (22.9%) showed abnormal levels of urea. The concordance Kappa coefficient for renal deterioration defined only by urea and creatinine above the cutoff value was 0.49 (p ⬍ 0.001). Eighteen-month free-DHF rehospitalization survival was 35% for patients with RD compared with 60% for those without RD (log rank test p ⫽ 0.0086). Patients with RD had a higher rate of previous HF (89 vs 78%, p ⫽ 0.041), more peripheral hypoperfusion (12.5 vs 4.1%, p ⫽ 0.020), lower EF (36.4 ⫾ 17.2 vs 41.1 ⫾ 19.6, p ⫽ 0.05) and more pro-BNP levels (8.681 ⫾ 9010 ng/mL vs 2943 ⫾ 2690 ng/mL, p ⬍ 0.001) than those without RD. In the Coxproportional hazard model, the presence of RD was significantly associated with the appearance of events during follow-up (HR ⫽ 1.7, CI95% ⫽ 1.14–2.60), with an adjusted HR for baseline differences of 1.77, CI95% ⫽ 1.16–2.69). Conclusion: The combined use of urea and creatinine during the admission of patients with DHF improve the ability of detection of RD. This finding was a strong long-term prognostic predictor.
Journal of Cardiac Failure Vol. 11 No. 6 Suppl. 2005
330
332
Fatal Myocardial Rupture after Acute MI Complicated by HF or LVSD: The VALIANT Trial F. Shamshad1, S. Kenchaiah2, P. V. Finn2, J. Soler-Soler3, L. Kober4, Y. Belenkov5, S. Varshavsky6, S. D. Solomon1; 1Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA; 2Division of Aging, Brigham and Women’s Hospital, Boston, MA; 3Servei de Cardiologia, Hospital General Universitari Vall d’Hebron, Barcelona, Spain; 4Department of Cardiology, Rigshospitalet, Copenhagen, Denmark; 5 Cardiology Research Institute, Moscow, Russian Federation; 6Evidence Clinical and Pharmaceutical Research, Los Altos, CA
Early Therapy with Nesiritide in Hospitalized Patients with Acute Decompensated Heart Failure Associated with Reduced Costs: A Markov Analysis Juan Blackburn1, Robert J. DiDomenico1, Daniel E. Hilleman2, Surrey M. Walton1, Glen T. Schumock1; 1Center for Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL; 2Medicine and Pharmacy Practice, Creighton University, Omaha, NE
Purpose: Cardiac rupture is a devastating complication of myocardial infarction (MI). We sought to identify risk factors for cardiac rupture in the first 30 days following high-risk MI. Methods: The VALsartan In Acute myocardial iNfarcTion (VALIANT) trial compared valsartan, captopril, or both in 14,703 high-risk patients post-MI. Cardiac rupture was identified in 45 (0.31%) patients (33 by autopsy, 8 by echo, 4 by surgical procedure), occurred 3 to 12 days (mean 9.8 ⫾ 6) after qualifying MI (free wall 82%, interventricular septum 11%, both 7%), and accounted for 7.6% (45/ 589) of deaths in the first 30 days. Results: Compared with the rest of the VALIANT cohort (n ⫽ 14,658), cardiac rupture was associated with older age, female sex, hypertension, Killip class ⱖ2, inferior wall MI, Q-wave MI, thrombolytic therapy, and heparin use (all P values ⬍0.05). Peak creatine kinase levels were similar in the 2 groups (11.0 ⫾ 7.8 vs. 10.0 ⫾ 6.0; P ⫽ 0.53). In age- and sex-adjusted analyses, Killip class ⱖ2, inferior wall MI, Q-wave MI, and concomitant use of heparin were associated with an increased risk of cardiac rupture. Rupture accounted for 24% of all autopsy proven deaths (n ⫽ 138) in the first 30 days. Conclusions: Our data suggest that higher Killip class, Q-wave MI, inferior MI, and heparin use are risk factors for cardiac rupture post-MI, in patients with heart failure or left ventricular systolic dysfunction. Incomplete ascertainment may result in an underestimate of the true incidence of rupture.
Age, yrs, mean ⫾ Female, % Hypertension Killip class ⱖ2, % Inferior wall MI Q-wave MI Heparin use
Rupture (n ⫽ 45)
Non-rupture (n ⫽ 14,658)
OR (95% CI)
P value
70.3 ⫾ 8.1 46.7 71.1 88.9 53.5 88.6 68.9
64.8 ⫾ 11.8 31.0 55.0 71.9 34.3 66.5 51.6
1.70 (0.88–3.27) 2.65 (1.04–6.76) 2.21 (1.21–4.03) 4.95 (1.94–12.66) 2.07 (1.10–3.90)
0.11 0.041 0.010 ⬍0.001 0.024
Introduction: Heart failure (HF) is a common clinical syndrome associated with morbidity, mortality, and a significant economic burden to patients, providers, and society. Acute decompensated heart failure (ADHF) leads to frequent hospital admissions, which account for up to 70% of the cost of HF. Nesiritide, a recombinant form of human b-type natriuretic peptide, may reduce downstream resource utilization and improve patient outcomes when used early in the treatment course. Hypothesis: The purpose of this study was to evaluate the costs and patient outcomes of nesiritide, given within 24 hours of hospitalization, versus standard therapy for the treatment of ADHF. Methods: A Markov model of ADHF was developed using TreeAge Pro Healthcare software (TreeAge Inc., Williamstown, MA). The model incorporates complications of therapy (atrial fibrillation and renal failure), location of inpatient care (intensive care unit, inpatient ward, or emergency department only), and hospital readmissions. Three stages of disease were included within each cycle of the model: well (survive ADHF hospitalization without suffering ADHF readmission), sick (survive ADHF hospitalization but suffer ADHF readmission), and death. Transition probabilities were calculated from previous published clinical trials. Estimates of hospital costs were obtained from a pilot study conducted at Creighton University Medical Center. The model was run over 6 cycles of one month each. The analysis was conducted from the hospital perspective. Results: Over 6 months, the total hospital costs (including all readmissions) for a patient treated with nesiritide or standard therapy were $9,787.65 and $10,914.28, respectively (2004 US dollars), a net decrease of $1,126.63 favoring nesiritide. Cost differences were largely attributable to a lower probability of readmission for patients receiving nesiritide. Survival at 6 months also favored nesiritide, with net gain of 0.081 years per patient over standard therapy. Conclusions: Our model predicts that nesiritide, given within 24 hours of hospitalization for ADHF, reduces overall costs and may improve survival over 6 months compared to standard therapy.
331
333
The Effect of Glycemic Control on Heart Failure Severity in Diabetics Geetha Bhat1,2, Jeff Stidam1, Margaret Dugan2, Kay Padgett2; 1Division of Cardiology, University of Louisville, Louisville, KY; 2Heart Failure & Cardiac Transplant Center, Jewish Hospital, Louisville, KY
Additive Effect of Increased Urea and Creatinine Levels Detected during Admission for Acute Decompensated Heart Failure in Relation to Long-Term Prognosis Stella M. Macin1, Juan P. Cimbaro Canella1, Eduardo R. Perna1, Valeria Franciosi1, Ariel Szyszko1, Jorge O. Kriskovich1, Augusto P. Bayol1, Walter Vargas Morales1, Bilda Gonzalez Arjol2; 1Heart Failure Clinic, Instituto de Cardiologia J. F. Cabral, Corrientes, Argentina; 2Laboratory, Instituto de Cardiologia J. F. Cabral, Corrientes, Argentina
Introduction: Glycosylated hemoglobin (Hb A1c) is an index of metabolic control in diabetes (D). Recent studies suggest that poor glycemic control in diabetic patients (pts) indicated by elevated Hb A1c levels may be associated with increased risk of heart failure (HF). Our goal was to investigate the association between Hb A1c level and severity of HF in advanced HF pts with D. Methods: Among 250 pts referred for cardiac transplantation, 71 consecutive pts with advanced HF and D underwent evaluation with blood glucose, serum creatinine, Hb A1c, BNP, cardiopulmonary exercise testing and right heart catheterizaton. Pts were divided into two groups based on Hb A1c ⱕ 6.5% (Group A, mean Hb A1c 5.6 ⫾ 0.7) and Hb A1c ⬎6.5% (Group B, mean Hb A1c 8.6 ⫾ 1.9). Results: Parameter (mean value) Age (years) Gender (male %) Peak oxygen consumption (V02) ml/kg/minute BNP (pg/ml) Pulmonary capillary wedge (PCW) pressure (mm Hg) Serum glucose (mg/dl) Creatinine BMI (kg/m2) % on Insulin
Hb A1c ⱕ 6.5% (Group A: n ⫽ 29)
Hb A1c ⬎ 6.5% (Group B: n ⫽ 42)
52.7 ⫾ 12.3 76 17.0 ⫾ 1.5
52.6 ⫾ 11.2 79 14.7 ⫾ 2.9
0.98 0.97 0.06
312.0 ⫾ 232.7 19.7 ⫾ 7.9
577.3 ⫾ 483.6 24.3 ⫾ 8.3
0.01* 0.06
124 ⫾ 59 1.4 ⫾ 0.5 27.9 ⫾ 8.0 35.7
201 ⫾ 100 1.3 ⫾ 0.4 29.8 ⫾ 6.2 71.4
0.001* 0.61 0.30 0.01*
P value
*p ⱕ 0.05 Conclusion: BNP was significantly elevated in diabetic pts with Hb A1c ⬎ 6.5%. In Group B there was a trend towards increased severity of symptoms and hemodynamics demonstrated by lower peak VO2 and higher PCW pressure. Significantly higher percentage of pts with elevated Hb A1c (group B) were on insulin compared to group A. Poor glycemic control in HF pts appears to have negative impact on functional capacity and severity of symptoms. Persistent glucose intolerance as shown by elevated Hb A1c ⬎ 6.5% may be contributing to increased fluid retention reflected by worse PCW pressure and significantly higher BNP in group B. Tight control of hyperglycemia may improve prognosis in diabetic pts with HF. The effect of improved glycemic control on clinical outcomes such as frequency of hospitalization and survival in advanced HF pts with D deserves further study.
Objective: To evaluate the prognostic role of early combined detection of elevated levels of urea and creatinine in patients hospitalized with decompensated heart failure (DHF) on the long-term outcome. Material and Methods: Two hundred and fortyone consecutive patients were included because of DHF, between nov/2002-nov/2003. At the time of admission the urea and creatinine cutoff value were selected using the ROC curve in order to detect combined events (death and rehospitalization due to DHF). Renal dysfunction (RD) was defined as a urea and/or creatinine level above the cutoff value. Results: The mean age was 65.4 ⫾ 11.6 years, 64% were male, and 42.3% had an ischemic etiology. During follow up, the incidence of events was 44.4% (107 patients). The area under the ROC curve to predicting events for urea and creatinine was 0.59 y 0.57, respectively. The cut-off, sensitivity and specificity were: urea 0.55 mg/dl, 57% and 63%, respectively; creatinine 1.17 mg/dl, 58% y 62%, respectively. During admission 144 (60.4%) patients showed renal deterioration, from which 82 patients (57%) had elevated both markers, 29 (20.1%) had only increased levels of creatinine, and 33 (22.9%) showed abnormal levels of urea. The concordance Kappa coefficient for renal deterioration defined only by urea and creatinine above the cutoff value was 0.49 (p ⬍ 0.001). Eighteen-month free-DHF rehospitalization survival was 35% for patients with RD compared with 60% for those without RD (log rank test p ⫽ 0.0086). Patients with RD had a higher rate of previous HF (89 vs 78%, p ⫽ 0.041), more peripheral hypoperfusion (12.5 vs 4.1%, p ⫽ 0.020), lower EF (36.4 ⫾ 17.2 vs 41.1 ⫾ 19.6, p ⫽ 0.05) and more pro-BNP levels (8.681 ⫾ 9010 ng/mL vs 2943 ⫾ 2690 ng/mL, p ⬍ 0.001) than those without RD. In the Coxproportional hazard model, the presence of RD was significantly associated with the appearance of events during follow-up (HR ⫽ 1.7, CI95% ⫽ 1.14–2.60), with an adjusted HR for baseline differences of 1.77, CI95% ⫽ 1.16–2.69). Conclusion: The combined use of urea and creatinine during the admission of patients with DHF improve the ability of detection of RD. This finding was a strong long-term prognostic predictor.