CA125-Guided Diuretic Treatment Versus Usual Care in Patients With Acute Heart Failure and Renal Dysfunction.

BACKGROUND: The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation. METHODS: This multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-guided group (n = 79) and in clinical evaluation in the usual-care group (n = 81). Changes in estimated glomerular filtration rate (eGFR) at 72 and 24 hours were the co-primary endpoints, respectively. RESULTS: The mean age was 78 ± 8 years, the median amino-terminal pro-brain natriuretic peptide was 7765 pg/mL, and the mean eGFR was 33.7 ± 11.3 mL/min/1.73m2. Over 72 hours, the CA125-guided group received higher furosemide equivalent dose compared to usual care (P = 0.011), which translated into higher urine volume (P = 0.042). Moreover, patients in the active arm with CA125 >35 U/mL received the highest furosemide equivalent dose (P <0.001) and had higher diuresis (P = 0.013). At 72 hours, eGFR (mL/min/1.73m2) significantly improved in the CA125-guided group (37.5 vs 34.8, P = 0.036), with no significant changes at 24 hours (35.8 vs 39.5, P = 0.391). CONCLUSION: A CA125-guided diuretic strategy significantly improved eGFR and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction.

Length of stay and risk of very early readmission in acute heart failure.

INTRODUCTION AND OBJECTIVES: In patients admitted for acute heart failure (AHF), optimal length of stay (LOS) remains controversial. Longer hospitalizations are associated with worse prognosis, but little is known about short hospitalizations. The aim of this work was to evaluate the relationship between LOS and the risk of short-term readmission in patients discharged after a hospitalization for AHF. METHODS: We included 2110 consecutive patients. The independent associations between LOS and unplanned 10, 15 and 30-day readmissions were evaluated by Cox regression analysis adjusted for competing events. LOS was categorized as LOS1: ≤4days, LOS2: 5-7days, LOS3: 8-10days, and LOS4: >10days. RESULTS: The mean age was 73±11years and 52.6% exhibited left ventricle ejection fraction≥50%. The median (IQR) LOS was 7 (5-11) days. At 10, 15 and 30-day follow-up, 130 (6.2%), 181 (8.6%), and 282 (13.4%) unplanned readmissions were registered. Rates of 10 and 15-day readmission among LOS categories showed a J-shaped pattern with lower rates for those in LOS2 and higher at the both extremes (p=0.001). At 30-day, only longer stays showed higher rates of readmission (p=0.002). In the multivariate analysis, the U-shaped curve remained significant for 10 and 15-day readmissions (p<0.05). Compared to LOS2, LOS1, LOS3 and LOS4 showed about two-fold increased risk. At 30-day only longer stays showed a borderline and modest increase of risk. CONCLUSIONS: Shorter and longer stays are associated with the risk of very early readmissions after an episode of AHF. These associations are marginal for 30-day readmissions.

Diuretic Strategies in Acute Heart Failure and Renal Dysfunction: Conventional vs Carbohydrate Antigen 125-guided Strategy. Clinical Trial Design.

INTRODUCTION AND OBJECTIVES: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. METHODS: Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days. RESULTS: The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. CONCLUSIONS: We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses.

Carbohydrate Antigen-125-Guided Therapy in Acute Heart Failure: CHANCE-HF: A Randomized Study.

OBJECTIVES: This study sought to evaluate the prognostic effect of carbohydrate antigen-125 (CA125)-guided therapy (CA125 strategy) versus standard of care (SOC) after a hospitalization for acute heart failure (AHF). BACKGROUND: CA125 has emerged as a surrogate of fluid overload and inflammatory status in AHF. After an episode of AHF admission, elevated values of this marker at baseline as well as its longitudinal profile relate to adverse outcomes, making it a potential tool for treatment guiding. METHODS: In a prospective multicenter randomized trial, 380 patients discharged for AHF and high CA125 were randomly assigned to the CA125 strategy (n = 187) or SOC (n = 193). The aim in the CA125 strategy was to reduce CA125 to ≤35 U/ml by up or down diuretic dose, enforcing the use of statins, and tightening patient monitoring. The primary endpoint was 1-year composite of death or AHF readmission. Treatment strategies were compared as a time to first event and longitudinally. RESULTS: Patients allocated to the CA125 strategy were more frequently visited, and treated with ambulatory intravenous loop diuretics and statins. Likewise, doses of oral loop diuretics and aldosterone receptor blockers were more frequently modified. The CA125 strategy resulted in a significant reduction of the primary endpoint, whether evaluated as time to first event (66 events vs. 84 events; p = 0.017) or as recurrent events (85 events vs. 165 events; incidence rate ratio: 0.49; 95% confidence interval: 0.28 to 0.82; p = 0.008). The effect was driven by significantly reducing rehospitalizations but not mortality. CONCLUSIONS: The CA125 strategy was superior to the SOC in terms of reducing the risk of the composite of 1-year death or AHF readmission. This effect was mainly driven by significantly reducing the rate of rehospitalizations. (Carbohydrate Antigen-125-guided Therapy in Heart Failure [CHANCE-HF]; NCT02008110).

Isolated Partial Congenital Absence of the Pericardium: A Familial Presentation.

Congenital defects of the pericardium are uncommon heart abnormalities. Most of the patients are asymptomatic and are usually diagnosed incidentally. Complications are more common in partial absence than in complete absence of the pericardium; thus, this congenital defect should be identified because of the associated risk of sudden death. We report the first mention in the literature, to our knowledge, of a 3-generation familial presentation of isolated congenital partial absence of the pericardium with similar physical examination and radiological findings.

Prognostic effect of carbohydrate antigen 125-guided therapy in patients recently discharged for acute heart failure (CHANCE-HF). Study design.

INTRODUCTION AND OBJECTIVES: Morbidity and mortality after admission for acute heart failure remain prohibitively high. In that setting, plasma levels of antigen carbohydrate 125 have shown to correlate with the severity of fluid overload and the risk of mortality and readmission. Preliminary data suggests a potential role of antigen carbohydrate 125 to guide therapy. The objective of this study is to evaluate the prognostic effect of an antigen carbohydrate 125-guided management strategy vs standard therapy in patients recently discharged for acute heart failure. METHODS: This is a multicenter, randomized, single-blind, efficacy trial study of patients recently discharged from acute heart failure (< 180 days), New York Heart Association functional class II-IV and antigen carbohydrate 125 > 35 U/ml. A randomization scheme was used to allocate participants (in a 1:1 ratio) to receive therapy guided by antigen carbohydrate 125 (aiming to keep normal values) or standard treatment. Mainly, antigen carbohydrate 125-guided therapy is focused on the frequency of monitoring and titration of decongestive therapies and statins. As of December 10, 2013, there were 383 patients enrolled. The primary outcome was the composite of 1-year all-cause mortality or rehospitalization for acute heart failure. Analysis was planned to be intention-to-treat. CONCLUSIONS: Discovering novel therapeutic strategies or finding better ways of optimizing established treatments have become a health care priority in heart failure. This study will add important knowledge about the potential of antigen carbohydrate 125 as a management tool for monitoring and titration of therapies where optimal utilization has not been well defined, such as diuretics and statins. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02008110.

Improvement in risk stratification with the combination of the tumour marker antigen carbohydrate 125 and brain natriuretic peptide in patients with acute heart failure.

AIM: Elevated brain natriuretic peptide (BNP) and tumour marker antigen carbohydrate 125 (CA125) levels have shown to be associated with higher risk for adverse outcomes in patients with acute heart failure (AHF). Nevertheless, no attempt has been made to explore the utility of combining these two biomarkers. We sought to assess whether CA125 adds prognostic value to BNP in predicting 6-month all-cause mortality in patients with AHF. METHODS AND RESULTS: We analysed 1111 consecutive patients admitted for AHF. Antigen carbohydrate 125 (U/mL) and BNP (pg/mL) were measured at a median of 72 +/- 12 h after instauration of treatment. Antigen carbohydrate 125 and BNP were dichotomized based on proposed prognostic cutpoints, and a variable with four categories was formed (BNP-CA125): C1 = BNP < 350 and CA125 < 60 (n = 394); C2 = BNP > or = 350 and CA125 < 60 (n = 165); C3 = BNP < 350 and CA125 > or = 60 (n = 331); and C4 = BNP > or = 350 and CA125 > or = 60 (n = 221). The independent association between BNP-CA125 and mortality was assessed with the Cox regression analysis, and their added predictive ability tested by the integrated discrimination improvement (IDI) index. At 6 months, 181 deaths (16.3%) were identified. The cumulative rate of mortality was lower for patients in C1 (7.8%), intermediate for C2 and C3 (17.8% and 16.9%, respectively), and higher for C4 (37.2%), and P-value for trend <0.001. After adjusting for established risk factors, the highest risk was observed when both biomarkers were elevated (C4 vs. C1: HR = 4.05, 95% CI = 2.54-6.45; P < 0.001) and intermediate when only one of them was elevated: (C2 vs. C1: HR = 1.71, 95% CI = 1.00-2.93; P = 0.050) and (C3 vs. C1: HR = 2.10, 95% CI = 1.30-3.39; P = 0.002). Moreover, when CA125 was added to the clinical model + BNP, a 10.4% (P < 0.0001) improvement in the IDI (on the relative scale) was found. CONCLUSION: In patients admitted with AHF, CA125 added prognostic value beyond the information provided by BNP, and thus, their combination enables better 6-month risk stratification.

[Prognostic value of the left ventricular ejection fraction in patients with acute heart failure]. / Valor pronóstico de la fracción de eyección del ventrículo izquierdo en pacientes con insuficiencia cardíaca aguda.

BACKGROUND AND OBJECTIVE: The relation between left ventricular ejection fraction (LVEF) and prognosis in patients with heart failure is controversial. The aim of this study was to determine the relation of LVEF in long-term mortality and readmissions for acute heart failure in a non-selected population of patients admitted with acute heart failure (AHF). PATIENTS AND METHOD: We included 507 patients admitted consecutively for AHF in a cardiology department of a single-centre. LVEF was assessed with transthoracic echocardiography during hospitalization. All-cause mortality and readmission for AHF were selected as primary and secondary endpoints, respectively. The independent association between LVEF and endpoints was assessed with traditional Cox regression analysis for all-cause mortality and Cox regression for competing risks for readmission for AHF. RESULTS: 47% of patients exhibited LVEF > or = 50%. During a median follow-up of one year, 151 (30%) deaths and 139 (27%) readmissions for AHF were observed. Mortality rates were higher in patients with LVEF < 50% (34 vs 25%; p = 0.028) and no differences were observed for readmissions for AHF (26 vs 29%, p = 0.510). In multivariate analysis, after adjustment for traditional risk factors, patients with LVEF < 50% did not show higher risk of mortality (hazard ratio [HR] = 1.08; 95% confidence interval [CI], 0.76-1.57; p = 0.645) or readmissions for AHF (HR = 1.00; 95% CI, 0.68-1.47; p = 1). CONCLUSIONS: Patients with preserved LVEF constitute a substantial proportion of patients with AHF, exhibiting similar mortality and readmissions risks compared with patients with depressed LVEF.

A practical approach with outcome for the prognostic assessment of non-ST-segment elevation chest pain and normal troponin.

Patients with non-ST-elevation chest pain constitute a heterogeneous population. Our aim is to compare the outcome of patients with chest pain, non-ST-segment deviation, and normal troponin, categorized using a risk score, with that of patients with ST depression or troponin increase. A total of 1,449 patients with non-ST-elevation chest pain were evaluated. A validated risk score (using pain characteristics and risk factors) was applied to patients without ST depression or troponin increase. Accordingly, 4 risk categories were defined: group 1, no troponin increase, no ST depression, and risk score <3 points (n = 633); group 2, no troponin increase, no ST depression, but risk score > or = 3 points (n = 158); group 3, no troponin increase, ST depression (n = 106); and group 4, troponin increase (n = 552). Median follow-up was 26 months, and the end point was death or myocardial infarction. Group 1 experienced fewer events at 30 days (1.7%, p = 0.0001) and long-term follow-up (9.4%, p = 0.0001) than groups 2 (10.8% and 26%), 3 (6.6% and 30%), and 4 (9.5% and 25%). Kaplan-Meier curves overlapped among groups 2, 3, and 4, whereas group 1 showed a flatter curve (p = 0.0001). Using multivariate analysis, risk group (group 1 vs remaining groups) predicted 30-day (p = 0.0003) and long-term (p = 0.0001) outcome. There were no differences among groups 2, 3, and 4. In conclusion, application of a risk score to patients without troponin increase or ST deviation identified a high-risk group with prognosis similar to that of patients with troponin increase or ST depression and affords a practical classification for the full spectrum of non-ST-elevation chest pain.

Prognostic usefulness of white blood cell count on admission and one-year outcome in patients with non-ST-segment elevation acute chest pain.

Little is known about the prognostic value of leukocyte count on admission for patients with chest pain. In total, 1,461 patients who presented to the emergency department with non-ST-segment elevation chest pain were studied by clinical history, electrocardiography, serial troponin I determination, and leukocyte count on admission. End points were 1-year mortality and major events (mortality or infarction). Overall patient distribution by quartiles of leukocyte count showed increased mortality (6%, 7%, 6%, and 17%, p = 0.0001) and major events (13%, 13%, 15%, and 24%, p = 0.0001) in the fourth quartile. After adjustment for other risk factors, the fourth quartile cut-off value (>10,000 cells/ml) predicted mortality (hazard ratio 2.0, 95% confidence interval 1.4 to 2.8, p = 0.0001) but not major events (p = 0.07). When analysis was performed to assess troponin status, in the subgroup with increased troponin (n = 634, 16% mortality), a leukocyte count >10,000 cells/ml was related to mortality (hazard ratio 2.2, 95% confidence interval 1.5 to 3.4, p = 0.0001). However, in the subgroup with normal troponin levels (n = 827, 4.2% mortality), there were no differences in mortality between patients with or without a leukocyte count >10,000 cells/ml (4.4% vs 4.2%, p = 0.8), with survival curves showing a tight overlap (p = 0.9). Further, in the subgroup with normal troponin levels, leukocyte count was not significantly different between patients with or without ST depression (7,969 +/- 2,171 vs 8,108 +/- 2,356 cells/ml, p = 0.6) and was not associated with mortality in patients with ST depression (p = 0.7). In conclusion, leukocyte count on admission is predictive of mortality in patients with chest pain and non-ST-segment elevation myocardial infarction. However, in the absence of myocardial necrosis, leukocyte count lacks prognostic value.

Usefulness of early exercise testing and clinical risk score for prognostic evaluation in chest pain units without preexisting evidence of myocardial ischemia.

We investigated whether the result of early exercise testing yields prognostic information in addition to that afforded by a clinical risk score in patients who present with chest pain in the emergency department. The study group consisted of 340 patients without preexisting evidence of myocardial ischemia. A clinical risk score was calculated. Primary (mortality or myocardial infarction) and secondary (mortality, myocardial infarction, or rehospitalization due to unstable angina) end points at 1 year were defined. Patients with a positive exercise test result underwent invasive management. Frequencies of primary (7.4% vs 2.1%, p = 0.06) and secondary (9.3% vs 2.8%, p = 0.04) end points and risk score (1.6 +/- 1.0 vs 1.0 +/- 0.9 points, p = 0.0001) were higher in patients with a positive exercise test result. However, in multivariate analysis, clinical risk score was the only independent predictor for the primary (hazard ratio 2.0, 95% confidence interval 1.2 to 3.2, p = 0.004) and secondary (hazard ratio 1.9, 95% confidence interval 1.2 to 2.9, p = 0.003) end points. In conclusion, if a policy of invasive management is implemented for patients with positive exercise test results, the clinical risk score constitutes the main prognostic predictor of 1-year outcome.

New risk score for patients with acute chest pain, non-ST-segment deviation, and normal troponin concentrations: a comparison with the TIMI risk score.

OBJECTIVES: The purpose of this research was to develop a risk score for patients with chest pain, non-ST-segment deviation electrocardiogram (ECG), and normal troponin levels. BACKGROUND: Prognosis assessment in this population remains a challenge. METHODS: A total of 646 consecutive patients were evaluated by clinical history (risk factors and chest pain score according to pain characteristics), ECG, and early exercise testing. ST-segment deviation and troponin elevation were exclusion criteria. The primary end point was mortality or myocardial infarction at one year. The secondary end point was mortality, myocardial infarction, or urgent revascularization at 14 days (similar to the Thrombolysis In Myocardial Infarction [TIMI] risk score). RESULTS: Primary and secondary end point rates were 6.7% and 5.4%. A risk score was constructed using the variables related to the primary end point: chest pain score > or =10 points (hazard ratio [HR] = 2.5; 1 point), > or =2 pain episodes in last 24 h (HR = 2.2; 1 point), age > or =67 years (HR = 2.3; 1 point), insulin-dependent diabetes mellitus (HR = 4.2; 2 points), and prior percutaneous transluminal coronary angioplasty (HR = 2.2; 1 point). Patients were classified into five categories of risk (p = 0.0001): 0 points, 0% event rate; 1 point, 3.1%; 2 points, 5.4%; 3 points, 17.6%; > or =4 points, 29.6%. The accuracy of the score was greater than that of the TIMI risk score for the primary (C index of 0.78 vs. 0.66, p = 0.0002) and secondary (C index of 0.70 vs. 0.66, p = 0.1) end points. CONCLUSIONS: Patients presenting with chest pain despite no ST-segment deviation or troponin elevation show a non-negligible rate of events at one year. A risk score derived from this specific population allows more accurate stratification than when using the TIMI risk score.