Prognostic value of cystatin C on admission in heart failure with preserved ejection frac…

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Pulmonary hypertension in heart failure.

J Card Fail. 2010 Jun;16(6):461-74

Authors: Guglin M, Khan H

BACKGROUND: Pulmonary hypertension occurs in 60% to 80% of patients with heart failure and is associated with high morbidity and mortality. METHODS AND RESULTS: Pulmonary artery pressure correlates with increased left ventricular end-diastolic pressure. Therefore, pulmonary hypertension is a common feature of heart failure with preserved as well as reduced systolic function. Pulmonary hypertension is partially reversible with normalization of cardiac filling pressures. Pulmonary vasculature remodeling and vasoconstriction create a second component, which does not reverse immediately, but has been shown to improve with vasoactive drugs and especially with left ventricular assist devices. CONCLUSION: Many drugs used for idiopathic pulmonary arterial hypertension are being considered as treatment options for heart failure-related pulmonary hypertension. This is of particular significance in the heart transplant population. Randomized clinical trials with interventions targeting heart failure patients with elevated pulmonary artery pressure would be justified.

PMID: 20610227 [PubMed - indexed for MEDLINE]

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A cost-saving strategy for inpatient management of advanced decompensated heart failure patients: the Cardiomyopathy Unit.

J Card Fail. 2009 Jun;15(5):428-34

Authors: Gregory D, Ordway LJ, McGillivray M, Konstam MA, Denofrio D

BACKGROUND: This article analyzes the relative costs and revenues of the Tufts Medical Center Cardiomyopathy Unit (CMU), a recent innovation for grouping and managing advanced decompensated heart failure patients. METHODS AND RESULTS: We selected a retrospective sample of all patients with the primary diagnosis of heart failure, primary procedure of pulmonary artery catheterization, and with no other hospitalization procedures, admitted to Tufts Medical Center between 2000 and 2006. Regression models were used to estimate the cost for the intervention group and controls. Propensity analysis was used to test for selection bias in the comparison groups. We identified 114 hospitalizations meeting these criteria. Patients in the CMU group were well-balanced compared with controls with respect to demographic and clinical variables. Estimated direct medical costs for CMU and control groups were $11,817 (95% CI $7678-$16,106) and $17,236 (95% CI $11,199-$23,493), respectively. A similar pattern of cost differentials was displayed among propensity-matched sample groups. Net revenue was $12,609 (95% CI $9578-$16,845) and $15,627 (95% CI $11,871-$20,877) in the CMU and control groups, respectively. CONCLUSIONS: The inpatient CMU may offer a lower cost and higher contribution margin alternative for the management of advanced heart failure patients requiring hemodynamic monitoring without other major inpatient procedures.

PMID: 19477403 [PubMed - indexed for MEDLINE]

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Six minute walk test predicts long-term all-cause mortality and heart failure rehospitalization in African-American patients hospitalized with acute decompensated heart failure.

J Card Fail. 2009 Mar;15(2):130-5

Authors: Alahdab MT, Mansour IN, Napan S, Stamos TD

BACKGROUND: The prognostic value of the 6-minute walk test (6MWT) has been described in patients with heart failure (HF); however, limited data are available in an African-American (AA) population. We prospectively evaluated the usefulness of the 6MWT in predicting mortality and HF rehospitalization in AA patients with acute decompensated HF. METHODS AND RESULTS: Two hundred AA patients (63.1% men, mean age 55.7 +/- 12.9 years) with acute decompensated HF were prospectively studied. Patients were followed to assess 40-month all-cause mortality and 18-month HF rehospitalization. The median distance walked on the 6MWT was 213 m. Of the 198 patients with available mortality data, 59 patients (29.8%) died. Of the 191 patients with available rehospitalization data, 114 (59.7%) were rehospitalized for worsening HF. For patients who walked <or=200 m during the 6MWT, mortality was 41% compared with 19% in patients who walked >200 m (P = .001). For patients who walked <or=200 m during the 6MWT, HF rehospitalization was 68% compared with 52% in those who walked >200 m (P = .027). Multivariate Cox regression analysis showed that 6MWT distance <or=200 m was the strongest predictor of mortality (adjusted hazard ratio [HR], 2.14; confidence interval [CI], 1.20 to 3.81; P = .01) and HF rehospitalization (adjusted HR, 1.62; CI, 1.10 to 2.39; P = .015). CONCLUSIONS: In AA patients hospitalized with acute decompensated HF, 6MWT strongly and independently predicts long-term all-cause mortality and HF rehospitalization.

PMID: 19254672 [PubMed - indexed for MEDLINE]

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The PROTECT pilot study: a randomized, placebo-controlled, dose-finding study of the adenosine A1 receptor antagonist rolofylline in patients with acute heart failure and renal impairment.

J Card Fail. 2008 Oct;14(8):631-40

Authors: Cotter G, Dittrich HC, Weatherley BD, Bloomfield DM, O’Connor CM, Metra M, Massie BM,

BACKGROUND: Rolofylline, an adenosine A(1) receptor antagonist, facilitates diuresis and preserves renal function in patients with acute heart failure (AHF) with renal impairment. Although not powered around any specific hypothesis, this pilot study was designed to identify an efficacious dose while refining inclusion criteria and end points. METHODS: A total of 301 patients hospitalized for AHF with an estimated creatinine clearance of 20 to 80 mL/min and elevated natriuretic peptide levels were enrolled within 24 hours of presentation to placebo or rolofylline 10, 20, or 30 mg administered as 4-hour infusions for 3 days in addition to intravenously administered loop diuretics. Post hoc analyses for end points chosen for subsequent Phase III studies were performed. RESULTS: Compared with placebo, rolofylline produced trends toward greater proportions of patients with marked or moderately improved dyspnea and fewer patients with worsening heart failure or renal function. Serum creatinine increased in patients receiving placebo and remained stable or tended to decrease in those receiving rolofylline. On day 14 the absolute differences between placebo and rolofylline for change in creatinine increased with increasing rolofylline dose, reflecting the lesser increase in creatinine in rolofylline-treated patients (r = -0.12, P = .030). Treatment with 30 mg, the dose selected for the pivotal trials, was associated with a trend toward reduced 60-day mortality or readmission for cardiovascular or renal cause (hazard ratio, 0.55; 95% confidence interval, 0.28-1.04). CONCLUSION: These results demonstrate that adenosine A(1) receptor blockade with rolofylline can prevent renal impairment in patients with AHF and may positively affect acute symptoms and 60-day outcome. A 2000-patient trial of this agent is now under way.

PMID: 18926433 [PubMed - indexed for MEDLINE]

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The cost of medical management in advanced heart failure during the final two years of life.

J Card Fail. 2008 Oct;14(8):651-8

Authors: Russo MJ, Gelijns AC, Stevenson LW, Sampat B, Aaronson KD, Renlund DG, Ascheim DD, Hong KN, Oz MC, Moskowitz AJ, Rose EA, Miller LW,

OBJECTIVE: To examine patterns of resource use and the cost of care for patients with advanced heart failure treated with medical management (MM) during the final 2 years of life. METHODS AND RESULTS: The study population (n=47, mean age 70.4 years+/-7.06) included patients randomized to the MM arm of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. Inpatient and outpatient use data were obtained from the clinical dataset and Centers for Medicare and Medicaid Services (beginning January 1, 1998). Cost and resource use were tracked from the date of death (t(d)) backward in 3-month intervals (eg, t(d-1), t(d-2)). In the primary analysis, costs were summed across intervals. The mean cost of MM in the final 2 years of life was $156,169, with 50.5% ($78,880.39) expended in the final 6 months. The mean quarterly cost increased (P < .01) 4.9-fold from t(d-8) ($8,816 +/- $14,270) to t(d-1) ($42,836 +/- $41,407). The number of inpatient days increased (P < .01) 6.6-fold from 3.8+/-4.7 days to 22.2+/-23.5 days during the same time intervals. CONCLUSION: This current economic analysis extends on previous findings by demonstrating that medical therapy in advanced and end-stage heart failure is associated with significant costs and resource consumption; these costs and resource consumption increase significantly as death approaches.

PMID: 18926436 [PubMed - indexed for MEDLINE]

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Outcomes of volume-overloaded cardiovascular patients treated with ultrafiltration.

J Card Fail. 2008 Aug;14(6):515-20

Authors: Jaski BE, Romeo A, Ortiz B, Hoagland PM, Stone M, Glaser D, Thomas L, Walsh C, Smith SC

BACKGROUND: Ultrafiltration (UF) can rapidly and predictably remove extracellular and intravascular fluid volume. To date, assessment of UF in patients with cardiovascular disease has been confined to short- and medium-term studies in patients with a principal diagnosis of acute heart failure. METHODS: In-hospital and long-term outcomes were reviewed from consecutive patients with cardiovascular disorders and recognized pulmonary and systemic volume overload treated with a simplified UF system with the capability for peripheral venovenous access. Trained abstractors reviewed both paper and electronic medical records. Patients with a principal diagnosis of heart failure versus other primary hospital discharge diagnoses were identified according to International Classification of Diseases, 9th Revision standards by independent coders. RESULTS: For a period of 43 months, 100 patients (76 male/24 female, 65 +/- 14.0 years of age, systolic dysfunction 64%) were treated with UF during 130 hospitalizations. Baseline systolic blood pressure was 119 +/- 23 mm Hg. Before UF, 53% were receiving intravenous vasoactive therapy. By using UF, 7.1 +/- 3.9 L of ultrafiltrate were removed during 2.0 +/- 1.2 treatments per hospitalization. Baseline creatinine was 1.8 +/- 0.8 and 1.9 +/- 1.2 (not significant) at discharge. Of the 15 in-hospital deaths, 14 occurred during the initial hospitalization. Left ventricular dysfunction was related to 13 (87%) of the 15 deaths; no deaths were related to UF use. In hospitalizations with a principal diagnosis of heart failure (n = 79), in-hospital mortality was 7.6% compared with an ADHERE risk tree estimated mortality of 7.5%. Multivariate logistic regression identified a trend for decreased systolic blood pressure to predict patient initial hospitalization mortality (P = .06). Kaplan-Meier survivals for all patients were 71% at 1 year and 67% at 2 years. Cox regression found decreased systolic blood pressure as a predictor of long-term mortality (P = .025). Total volume of ultrafiltrate removed, ejection fraction, history of coronary artery disease, creatinine clearance, gender, age, and principal diagnosis of heart failure were not significantly associated with long-term mortality. CONCLUSION: This series extends the spectrum of patients previously reported to be treated with UF. Despite marked volume overload, UF-treated patients with a principal diagnosis of heart failure had inpatient outcomes similar to the ADHERE registry. UF should be considered for a broad range of patients who present with volume overload.

PMID: 18672200 [PubMed - indexed for MEDLINE]

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The effects of nesiritide on renal function and diuretic responsiveness in acutely decompensated heart failure patients with renal dysfunction.

J Card Fail. 2008 May;14(4):267-75

Authors: Owan TE, Chen HH, Frantz RP, Karon BL, Miller WL, Rodeheffer RJ, Hodge DO, Burnett JC, Redfield MM

BACKGROUND: Strategies to preserve renal function and enhance diuretic responsiveness during therapy for heart failure (HF) are needed. We hypothesized that brain natriuretic peptide (nesiritide) added to standard HF therapy would preserve renal function and enhance diuretic responsiveness. METHODS: Patients with HF with underlying renal dysfunction who were admitted with volume overload were randomized to standard therapy with nesiritide (2 mug/kg bolus; 0.01 mug/kg/min for 48 hours) or without nesiritide. Patients requiring intravenous vasodilator or inotropic therapy for rapid symptom relief were ineligible. In all patients, diuretics were administered according to a standardized dosing algorithm. RESULTS: Patients (n = 72) had a mean creatinine level of 1.75 +/- 0.59 mg/dL. Patients receiving nesiritide had a lesser increase in creatinine (P = .048) and blood urea nitrogen (P = .02), but a greater reduction in blood pressure (P < .01). Nesiritide did not enhance diuretic responsiveness (P = .57) but increased 3'5' cyclic guanosine monophosphate and decreased endothelin more (P < .05 for both). There were no differences in the change in atrial natriuretic peptide, N-terminal pro-brain natriuretic peptide, plasma renin activity, angiotensin II, and aldosterone between groups. CONCLUSION: When used as adjuvant "renal protective" therapy in patients with HF with renal dysfunction, the recommended dose of nesiritide reduced blood pressure, did not seem to worsen renal function, and suppressed endothelin but did not enhance diuretic responsiveness or prevent activation of the renin-angiotensin-aldosterone system.

PMID: 18474338 [PubMed - indexed for MEDLINE]

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Inpatient initiation of beta-blockade plus nurse management in vulnerable heart failure patients: a randomized study.

J Card Fail. 2008 May;14(4):303-9

Authors: Krantz MJ, Havranek EP, Haynes DK, Smith I, Bucher-Bartelson B, Long CS

BACKGROUND: Predischarge beta-blocker initiation in hospitalized patients with heart failure due to reduced left ventricular ejection fraction (LVEF) is safe and improves adherence; improved outcomes with this approach have not been demonstrated in a randomized trial. This study compared 6-month rehospitalization rates among patients assigned to predischarge beta-blockade coupled with postdischarge nurse management (intervention) versus usual care. METHODS AND RESULTS: We randomized 64 patients with an LVEF </=0.40 to low-dose carvedilol coupled with nurse management or usual care. The nurse manager saw patients within 2 weeks of discharge, then biweekly until stable. Baseline characteristics reflected a vulnerable population (80% uninsured, 72% minorities, 80% unemployed or disabled), as did heart failure etiology (28% substance abuse, 27% ischemic, 19% hypertension, 17% idiopathic). Mean baseline LVEF was 0.23 in both groups. Among intervention patients at 6 -months, beta-blocker utilization was higher (96 vs. 48%, P < .001), mean New York Heart Association class improved (-1.44 vs. -0.77, P = .01), and total heart failure rehospitalizations were reduced by 84% (3 vs. 19, P = .02). A trend toward improved LVEF was also observed (+16 vs. +11 units, P = .17). CONCLUSION: Inpatient beta-blocker initiation coupled with nurse management improved outcomes among sociodemographically disadvantaged heart failure patients. Our results support a practice shift toward inpatient beta-blocker initiation with structured outpatient follow-up.

PMID: 18474343 [PubMed - indexed for MEDLINE]

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Safety and tolerability of angiotensin-converting enzyme inhibitor versus the combination of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker in patients with left ventricular dysfunction: a systematic review and meta-analysis of randomized controlled trials.

J Card Fail. 2008 Apr;14(3):181-8

Authors: Lakhdar R, Al-Mallah MH, Lanfear DE

BACKGROUND: The addition of an angiotensin receptor blocker (ARB) to an angiotensin-converting enzyme inhibitor (ACEI) in patients with heart failure remains controversial. A recent meta-analysis showed that the combination therapy reduces hospitalization without improved survival. Whether excess risk is associated with this strategy has not been fully explored. We sought to quantify the risk of adverse events of combination therapy (ACEI+ARB) versus ACEI alone. METHODS: MEDLINE, EMBASE, BIOSIS, and Cochrane databases were searched. Eligible studies were randomized, placebo-controlled trials of ACEI versus the combination of ACEI+ARB in patients with heart failure or left ventricular dysfunction. Included studies were reviewed to determine the frequency of adverse effects leading to discontinuation of therapy. RESULTS: Nine trials that enrolled 18,160 patients met the inclusion criteria. A total of 9199 patients received combination therapy, and 8961 patients received an ACEI only. Patients receiving combination therapy had an increased risk of developing any adverse effect by 2.3% (relative risk [RR] = 1.27, 95% confidence interval [CI] = 1.15-1.40, P < .00001, I(2) = 15.9%, number needed to harm [NNH] = 42), hypotension by 1.1% (RR = 1.91, 95% CI = 1.37-2.66, P = .0002, I(2) = 26.6%, NNH = 89), worsening renal function by 1% (RR = 2.12, 95% CI = 1.30-3.46, P = .003, I(2) = 67.3%, NNH = 100), and hyperkalemia by 0.6% (RR = 4.17, 95% CI = 2.31-7.53, P < .00001, I(2) = 0%, NNH = 149). There was no difference in angioedema (RR = 0.88, 95% CI = 0.43-1.80, P = .72, I(2) = 0%) or cough (RR = 0.84, 95% CI = 0.65-1.09, P = .19, I(2) = 0%). CONCLUSION: The current cumulative evidence suggests that patients with left ventricular dysfunction have an increased risk of adverse events leading to discontinuation on ACEI+ARB combination therapy compared with ACEI alone. This excess risk, coupled with a lack of consistent mortality benefit, suggests that ARBs should not routinely be added to ACEI therapy for left ventricular dysfunction. If chosen, the combination strategy may warrant closer patient monitoring to detect adverse effects.

PMID: 18381180 [PubMed - indexed for MEDLINE]

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