Since 1996 we used a stepwise regimen which included beraprost tablets or iloprost inhalation in the earlier stages of the disease and i.v. iloprost infusion in ...
The 7th Annual Scientific Meeting
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HFSA
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A Retrospective Analysis of Major Determinants of Heart Failure Mortality in Patients Receiving Both ACE Inhibitors and Beta-Blockers in Val-HeFT Inder S. Anand,1 Robert Glazer,2 Yann-Tong Chiang,2 Allen Hester,2 Nora Aknay,2 Jay N. Cohn3—1VA Medical Center, Minneapolis, MN; 2Novartis Pharmaceutical Corporation, East Hanover, NJ; 3University of Minnesota, Minneapolis, MN
Impact of Percutaneous Intervention on the Clinical Course and Outcomes in Diabetics with Coronary Heart Disease and Left Ventricular Dysfunction Ambika Bhaskaran,1 Robert M. Siegel,1 Neil Goldberg,2 Karl Moon,2 Sarah Scagnelli,2 Michelle E. Rhodes,1 Stephanie M. Christison,1 Jennifer C. Vermillion1—1Cardiovascular Research, Advanced Cardiac Specialists, Gilbert, AZ; 2Phoenix Memorial Hospital, Phoenix, AZ
Background: Valsartan (V) caused a 13.2% reduction in mortality and morbidity (M ⫹ M) in patients with moderate to severe heart failure (HF) in Val-HeFT. Posthoc analysis showed consistent beneficial effects for valsartan within cotherapy subgroups with the exception of the subgroup (N ⫽ 1610) receiving both an ACE-I and a beta-blocker (BB). These patients had the lowest annual mortality rate among the cotherapy subgroups (∼7%), but showed an increased M ⫹ M incidence with valsartan. The explanation of this unexpected finding is unknown. It has been hypothesized that there was an excessive neurohormonal blockade causing the adverse effect within this subgroup. Methods and Results: We evaluated the effects of V and placebo (P) on several determinants of HF M ⫹ M [brain natriuretic peptide (BNP), norepinephrine (NE), BUN, serum creatinine (Cr), and potassium (K), systolic blood pressure (SBP) and heart rate (HR)]. The change in these parameters from baseline to endpoint (last measurement) in V and P groups was determined separately for patients who died (Vd, Pd) and those who were alive (Va, Pa). The difference in the effect of V and P in the patients who died (Vd-Pd) and in those who were alive (Va-Pa) was compared in the subgroup of patients receiving ACE-I and BB. For all parameters, the effect of V (P-subtracted) was not significantly different between patients alive and patients who died with the exception of a paradoxically greater beneficial effect on BNP in patients who died (see Table). Conclusions: These data suggest that it is unlikely that excessive neurohormonal blockade was the cause of the unexpected adverse outcome observed in this subgroup. Change from Baseline to Endpoint - Patients Alive Va Number of patients⫹ 548 BNP (pg/ml) ⫺21.2 NE (pg/ml) 6.7 BUN (mg/dl) 4.67 Cr (mg/dl) 0.14 K (mEq/l) 0.06 SBP (mm Hg) ⫺7.1 HR (beats/min) ⫺0.4
Pa 620 ⫺2.9 28.5 2.59 0.08 ⫺0.09 ⫺3.2 0.8
Va-Pa
Change from Baseline to Endpoint - Patients who Died Vd
89 ⫺18.3 ⫺8.0 ⫺21.8 101.2 2.08* 6.66 0.07* 0.24 0.15* 0.16 ⫺3.9* ⫺7.6 ⫺1.2* 3.4
Pd 67 65.5 85.6 6.17 0.15 ⫺0.10 ⫺3.8 2.3
Vd-Pd ⫺73.5 15.6 0.48 0.09 0.26* ⫺3.8 1.1
P-value for (Va-Pa) vs (Vd-Pd) 0.027 0.460 0.582 0.569 0.114 0.590 0.099
Background: Approximately 35% of patients hospitalized with HF are diabetic. The prevalence increases further among patients with more severe HF, ranging from 47% to 86%. Hyperglycemia is known to induce cardiac remodeling and a vicious circle within which HF and insulin resistance contribute to each other. The most common etiology of HF in diabetics is Coronary Heart Disease (CHD). There is limited and conflicting data regarding the effectiveness of percutaneous coronary intervention (PCI) on survival and morbidity in diabetics with CHD and LV dysfunction (LVD). Objective: We evaluated our HF registry to determine the impact of PCI on immediate and long-term clinical outcomes in diabetics with advanced CHF (LVEF ⱕ35%). From 1/98 to 1/03, we performed PCI in 419 patients (mean age 65.2; 38% female) with diabetes and advanced CHF. Of these, 36% had prior MI; 32% had prior CABG and 41% had prior PCI. Additional co-morbidities included hypertension (78%), dyslipidemia (50.4%) and prior CVA (7.4%). Mean NYHA functional class was 3.2; diastolic dysfunction (DD) was seen in 69%. Mean global LVEF at presentation was 31.14%. Indications for PCI included acute MI (19.8%), unstable angina (36%), cardiogenic shock (1.4%), sudden death (1.4%), and objective evidence of inducible ischemia on stress testing (30%). Multivessel disease was present in 42.3%. The culprit lesion was ostial/proximal in 53%, implying large volume of potentially salvageable myocardium. Adjunctive IABP support was used in 29%; 68% received stents. Results: Procedural success was achieved in 401 (95.7%). The incidence of in-hospital adverse events (acute reclosure 0.7%; CABG 0.9%; death 0.7%) was low. At 1-year follow up, there was demonstrable improvement in symptoms and signs of CHF. Mean functional class improved to 1.7 (p ⫽ 0.002), diastolic dysfunction persisted in only 13% (p ⬍ 0.0001). Mean global LVEF rose to 41.39% (p ⫽ 0.000). The need for diuretics and intermittent inotropic support fell significantly (p ⬍ 0.0001). The incidence of ER visits (2.1%) and hospitalization (2.9%) for worsening CHF was low. The incidence of mortality (6.0%), target vessel revascularization (9.8%) and stroke (1.4%) were favorable. Conclusions: (1) In selected diabetic patients with ischemic CMP and advanced CHF, PCI was a safe and effective means of myocardial salvage, resulting in significant improvement in multiple functional and clinical parameters. (2) Procedural success was impressive despite a high prevalence of additional comorbidities at baseline. (3) At 1 year following revascularization, there was significant improvement in LV systolic and diastolic performance. This translated into improved functional class, low incidence of ER/hospital visits and low 1-year mortality. (4) Our experience demonstrates that percutaneous coronary revascularization strategies may be rewarding in diabetic patients with advanced CHF. Effective myocardial salvage is the key to improved eventfree and absolute survival in these patients.
⫹ Non-neurohormonal variables have higher number of pts; *p ⬍ 0.05
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Stepwise Therapeutic Regimen with Prostacyclin Analogs for Primary Pulmonary Hypertension: Hemodynamic Benefits and Impact on Patients Survival Michael Dandel,1 Dagmar Kemper,1 Hans Lehmkuhl,1 Roland Hetzer1— 1 Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum, Berlin, Germany
Prognostic Value of Hyponatremia in Hospitalized Patients with Worsening Heart Failure – Insights from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME - CHF) Liviu Klein,1 Wendy A. Gattis,2 Jeffrey D. Leimberger,2 Ileana L. Pina,3 Christopher M. O’Connor,2 Mihai Gheorghiade4—1Department of Medicine, Advocate Illinois Masonic Medical Center, Chicago, IL; 2Cardiovascular Division, Duke Clinical Research Institute, Durham, NC; 3Division of Cardiology, University Hospitals of Cleveland, Cleveland, OH; 4Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, IL
Background: Without treatment, patients with primary pulmonary hypertension (PPH) survive ⬍3 years after diagnosis. We assessed the outcome of PPH patients referred for transplantation (Tx) in order to evaluate the hemodynamical and survival benefits of pre-transplant prostanoid therapy. Methods: The analysis included 84 PPH patients referred for Tx between 1994-2002. Tx was performed in 35 patients (19 heart-lung and 16 doublelung). Since 1996 we used a stepwise regimen which included beraprost tablets or iloprost inhalation in the earlier stages of the disease and i.v. iloprost infusion in NYHA class IV patients, followed by Tx in those not responding to therapy. After initial right heart catheterization performed in all patients, those treated with prostanoids underwent further routine invasive hemodynamic monitoring at predefined time intervals. Routine echocardiographic monitoring and exercise testing were performed in all patients at different time intervals depending on the severity of PPH. Results: All patients which were treated prostanoids showed significant (p ⬍ 0.01) improvement in exercise capacity (VO2 max
and/or 6 min walk test), reduction in pulmonary vascular resistance, cardiac index increase, reduction of right ventricular (RV) diameters and RV ejection fraction increase. Among the 22 patients which were treated with i.v. iloprost infusion, 5 (22.7%) remained stable at NYHA Class II for more than 2 years. In 14 patients, which underwent neither prostanoid therapy (for various reasons) nor Tx (8 died before, 6 are still on the waiting list), the median survival after diagnosis was only 22 ⫾ 15 months. The other 70 patients, which were either treated with prostanoids prior to Tx or were transplanted without pre-Tx prostanoid treatment, showed a significantly longer (p ⬍ 0.001) median survival time after diagnosis (73.5 ⫾ 25.3 months). The 54 patients treated with prostanoids (19 transplanted, 35 not or not yet transplanted) had significantly higher survival rates (p ⬍ 0.01) than the 30 patients not treated with prostanoids (20 transplanted, 14 not or not yet transplanted). The 3-year actuarial survival after diagnosis was 81% in patients treated with prostanoids and 59,2% in those without prostanoids. The mortality rate on the Tx waiting list was 14.8% in the prostanoid group and 26.6% in the group without prostanoid treatment (p ⬍ 0.01). The 5-year actuarial survival after Tx was 50%. All 16 patients with double-lung Tx had normal RV function after Tx. Among the 27 patients treated at the present time with prostanoids (duration: 25.2 ⫾ 12.6 months), listing for Tx could be postponed in 26 patients, although the mean time after diagnosis reached already 58.0 ⫾ 54.4 months. Conclusions: A stepwise regimen with prostanoids improve and stabilize both the
hemodynamics and RV function in PPH patients. Since use of prostanoids increases the 3year actuarial survival after PPH diagnosis and reduces the mortality rate on the waiting list, it is an effective bridging-to-transplant therapy. Tx in combination with prior prostanoid administration provides important survival benefits for PPH patients.
In a post – hoc analysis we thought to describe the incidence of hyponatremia and its impact on mortality and rehospitalizations in hospitalized patients (pts.) with heart failure (HF) enrolled in the OPTIME – CHF trial. Methods: The OPTIME – CHF trial randomized 949 pts. with systolic dysfunction hospitalized for worsening HF and not requiring intravenous inotropic support to receive 48 – 72 hours of intravenous milrinone or placebo. Cox proportional hazards regression analysis was used to explore the relationship between baseline hyponatremia (Na ⱕ 136 mEq/l) and mortality at sixty days. Logistic regression was used to examine hyponatremia and rehospitalization or death at 60 days. Results: There were 256 pts. with Naⱕ136 mEq/l and 687 pts. with Na ⬎136 mEq/l. The results are showed in Table 1. Conclusions: Hyponatremia (Na ⱕ 136 mEq/l) is common in hospitalized pts. with worsening HF. After adjusting for baseline variables, the Cox regression analysis showed that baseline Na, when modeled linearly, predicts an increased mortality at sixty days: Na (per 5 mEq/l) has a Hazard Ratio of 0.75 with 95% CI 0.6 - 0.95, p ⫽ 0.018. Future treatments aimed at normalizing serum sodium might improve the survival and should be evaluated in randomized trials. Baseline characteristics and clinical outcomes in patients hospitalized with heart failure from the OPTIME in CHF Trial
Variable Age (years)* Male sex (%) Ischemic etiology of HF (%) NYHA Class III - IV (%) Elevated JVP (%) Pulmonary rales (%) Baseline HR (bpm)* Baseline SBP (mmHg)* Baseline DBP (mm Hg)* Baseline BUN (mg/dl)* Baseline Cr (mg/dl)* Mortality at 60 days (%) Rehospitalizations/ death at 60 days (%)
Baseline Na ⱕ 136 mEq/l - 256 pts. (27%)
Baseline Na ⬎136 mEq/l - 687 pts. (73%)
67 (53, 76) 68 55 96 72 83 84 (72, 96) 114 (100, 130) 70 (60, 78) 11.8 (7.1, 17.5) 1.4 (1.1, 1.8) 16% 42%
68 (57, 76) 66 50 92 66 81 84 (72, 96) 121 (108, 135) 70 (62, 80) 8.6 (6.1, 13.2) 1.3 (1.1, 1.7) 7% 33%
*Median, 25th, 75th **Log – rank statistic
p value 0.669 0.577 0.18 0.047 0.1157 0.444 0.5654 0.0001 0.015 0.0001 0.0172 0.0001** 0.017
