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).

Valor pronóstico a largo plazo del análisis completo de los índices de resonancia magnética cardiaca tras un infarto de miocardio con elevación del segmento ST / Long-term prognostic value of a comprehensive assessment of cardiac magnetic resonance indexes after an ST-segment elevation myocardial infarction

Introducción y objetivos. Se ha demostrado el valor pronóstico de varios índices de resonancia magnética cardiaca a medio plazo tras un infarto agudo de miocardio con elevación del segmento ST. La extensión de la necrosis transmural permite una predicción simple y exacta de viabilidad miocárdica. Sin embargo, se desconoce su valor pronóstico a largo plazo más allá de una completa evaluación clínica y por resonancia. Nuestra hipótesis es que la evaluación semicuantitativa de la extensión de la necrosis transmural es el mejor índice de resonancia para predecir el pronóstico a largo plazo tras un infarto con elevación del segmento ST. Métodos. Se realizó un estudio cuantitativo con resonancia a 206 pacientes consecutivos tras un infarto con elevación del segmento ST. También se evaluó semicuantitativamente (número de segmentos alterados, modelo de 17 segmentos) edema, contractilidad basal y tras dobutamina, perfusión de primer paso, obstrucción microvascular y extensión de la necrosis transmural. Resultados. Durante el seguimiento (mediana, 51 meses), 29 pacientes sufrieron un primer evento cardiaco adverso (8 muertes cardiacas, 11 infartos y 10 reingresos por insuficiencia cardiaca). Estos eventos se asociaron con mayor alteración de los índices de resonancia. Tras un ajuste multivariable, la extensión de la necrosis transmural fue el único índice de resonancia con asociación independiente con los eventos cardiacos adversos (razón de riesgos = 1,34 [1,19-1,51] por cada segmento con necrosis transmural > 50%; p < 0,001). Conclusiones. Un sencillo análisis semicuantitativo de la extensión de la necrosis transmural es el índice de resonancia cardiaca más potente para predecir el pronóstico a largo plazo tras un infarto agudo de miocardio con elevación del segmento ST (AU)

Introduction and objectives: A variety of cardiac magnetic resonance indexes predict mid-term prognosis in ST-segment elevation myocardial infarction patients. The extent of transmural necrosis permits simple and accurate prediction of systolic recovery. However, its long-term prognostic value beyond a comprehensive clinical and cardiac magnetic resonance evaluation is unknown. We hypothesized that a simple semiquantitative assessment of the extent of transmural necrosis is the best resonance index to predict long-term outcome soon after a first ST-segment elevation myocardial infarction. Methods: One week after a first ST-segment elevation myocardial infarction we carried out a comprehensive quantification of several resonance parameters in 206 consecutive patients. A semiquantitative assessment (altered number of segments in the 17-segment model) of edema, baseline and post-dobutamine wall motion abnormalities, first pass perfusion, microvascular obstruction, and the extent of transmural necrosis was also performed. Results: During follow-up (median 51 months), 29 patients suffered a major adverse cardiac event (8 cardiac deaths, 11 nonfatal myocardial infarctions, and 10 readmissions for heart failure). Major cardiac events were associated with more severely altered quantitative and semiquantitative resonance indexes. After a comprehensive multivariate adjustment, the extent of transmural necrosis was the only resonance index independently related to the major cardiac event rate (hazard ratio=1.34 [1.19-1.51] per each additional segment displaying >50% transmural necrosis, P<.001). Conclusions: A simple and non-time consuming semiquantitative analysis of the extent of transmural necrosis is the most powerful cardiac magnetic resonance index to predict long-term outcome soon after a first ST-segment elevation myocardial infarction (AU)

Predictors of cardiovascular magnetic resonance-derived microvascular obstruction on patient admission in STEMI.

BACKGROUND: Early stratification of patients according to the risk for developing microvascular obstruction (MVO) after ST-segment elevation myocardial infarction (STEMI) is desirable. We aimed to identify predictors of cardiovascular magnetic resonance (CMR)-derived MVO from clinical+ECG, laboratory and angiographic parameters available on admission. METHODS: Characteristics available on admission were documented in 97 STEMI patients referred for primary angioplasty. MVO was determined using contrast-enhanced CMR. RESULTS: MVO was present in 44 patients (45%). The C-statistic for predicting MVO was: clinical+ECG (.832), laboratory (.743), and angiographic parameters (.669). Adding laboratory to clinical+ECG information did not improve the C-statistic (.873 vs. .832, p=.2). Further addition of angiographic data (.904) improved the C-statistic of clinical+ECG (p=.04) but not of clinical+ECG and laboratory (p=.2). Independent predictors of MVO using clinical and ECG parameters were: Killip class >1 (OR 15.97 95%CI [1.37-186.76], p=.03), diabetes (OR 6.15 95%CI [1.49-25.39], p=.01), age <55years (OR 4.70 95%CI [1.56-14.17], p=.006), sum of ST-segment elevation >10mm (OR 4.5 95%CI [1.58-12.69], p=.005) and delayed presentation >3h (OR 3.80 95%CI [1.19-12.1], p=.02). A score was constructed assigning Killip class >1 2 points and the remaining indexes 1 point. The incidence of MVO increased with the score: 0 point: 8.7%; 1 point: 28.1%; 2 points: 71.4%; and 3+ points: 93% (p<.0001). CONCLUSIONS: MVO can be predicted using parameters already available on patient admission. We developed a clinical-ECG score allowing for early and reliable classification of STEMI patients according to the risk of MVO.

Long-term prognostic value of a comprehensive assessment of cardiac magnetic resonance indexes after an ST-segment elevation myocardial infarction.

INTRODUCTION AND OBJECTIVES: A variety of cardiac magnetic resonance indexes predict mid-term prognosis in ST-segment elevation myocardial infarction patients. The extent of transmural necrosis permits simple and accurate prediction of systolic recovery. However, its long-term prognostic value beyond a comprehensive clinical and cardiac magnetic resonance evaluation is unknown. We hypothesized that a simple semiquantitative assessment of the extent of transmural necrosis is the best resonance index to predict long-term outcome soon after a first ST-segment elevation myocardial infarction. METHODS: One week after a first ST-segment elevation myocardial infarction we carried out a comprehensive quantification of several resonance parameters in 206 consecutive patients. A semiquantitative assessment (altered number of segments in the 17-segment model) of edema, baseline and post-dobutamine wall motion abnormalities, first pass perfusion, microvascular obstruction, and the extent of transmural necrosis was also performed. RESULTS: During follow-up (median 51 months), 29 patients suffered a major adverse cardiac event (8 cardiac deaths, 11 nonfatal myocardial infarctions, and 10 readmissions for heart failure). Major cardiac events were associated with more severely altered quantitative and semiquantitative resonance indexes. After a comprehensive multivariate adjustment, the extent of transmural necrosis was the only resonance index independently related to the major cardiac event rate (hazard ratio=1.34 [1.19-1.51] per each additional segment displaying>50% transmural necrosis, P<.001). CONCLUSIONS: A simple and non-time consuming semiquantitative analysis of the extent of transmural necrosis is the most powerful cardiac magnetic resonance index to predict long-term outcome soon after a first ST-segment elevation myocardial infarction.

Cardiovascular magnetic resonance-derived intramyocardial hemorrhage after STEMI: Influence on long-term prognosis, adverse left ventricular remodeling and relationship with microvascular obstruction.

BACKGROUND: T2 weighted cardiovascular magnetic resonance (CMR) can detect intramyocardial hemorrhage (IMH) after ST-elevation myocardial infarction (STEMI). The long-term prognostic value of IMH beyond a comprehensive CMR assessment with late enhancement (LE) imaging including microvascular obstruction (MVO) is unclear. The value of CMR-derived IMH for predicting major adverse cardiac events (MACE) and adverse cardiac remodeling after STEMI and its relationship with MVO was analyzed. METHODS: CMR including LE and T2 sequences was performed in 304 patients 1 week after STEMI. Adverse remodeling was defined as dilated left ventricular end-systolic volume indexes (dLVESV) at 6 months CMR. RESULTS: During a median follow-up of 140 weeks, 47 MACE (10 cardiac deaths, 16 myocardial infarctions, 21 heart failure episodes) occurred. Predictors of MACE were ejection fraction (HR .95 95% CI [.93-.97], p=.001, per %) and IMH (HR 1.17 95% CI [1.03-1.33], p=.01, per segment). The extent of MVO and IMH significantly correlated (r=.951, p<.0001). dLVESV was present in 40% of patients. CMR predictors of dLVESV were: LVESV (OR 1.11 95% CI [1.07-1.15], p<.0001, per ml/m(2)), infarct size (OR 1.05 95% CI [1.01-1.09], p=.02, per %) and IMH (OR 1.54 95% CI [1.15-2.07], p=.004, per segment). Addition of T2 information did not improve the LE and cine CMR-model for predicting MACE (.744 95% CI [.659-.829] vs. .734 95% CI [.650-.818], p=.6) or dLVESV (.914 95% CI [.875-.952] vs. .913 95% CI [.875-.952], p=.9). CONCLUSIONS: IMH after STEMI predicts MACE and adverse remodeling. Nevertheless, with a strong interrelation with MVO, the addition of T2 imaging does not improve the predictive value of LE-CMR.

Serum heat shock protein 60 in acute heart failure: a new biomarker?

Heat shock protein 60 (HSP60) is a mitochondrial protein constitutively expressed in the majority of cells, and its expression is up-regulated by a variety of stressors. In heart failure, HSP60 is released from cardiomyocytes. The authors speculate that increased serum HSP60 (sHSP60) may be related to the severity of heart failure. This investigation sought to assess the association between sHSP60 and the composite end point of death/readmission in patients with acute heart failure (AHF). A total of 132 consecutive patients were admitted for AHF. The independent association between sHSP60 and the end point was assessed with Cox regression. During a median follow-up of 7 months (interquartile range, 3-14), 35 (26.5%) deaths, 40 (30.3%) readmissions, and 65 (49.2%) deaths/readmission were identified. Patients who exhibited the outcome showed higher median sHSP60 values (6.15 ng/mL [8.49] vs 4.71 ng/mL [7.55] P=.010). A monotonic increase in the incidence of the composite end point was observed when moving from lower to higher tertile (4.74, 4.76, and 6.98 per 10 patients-years of follow-up, P for trend <.001). After adjusting for established risk factors, only patients in the upper tertile showed an increased risk of death/readmission (hazard ratio, 2.63; 95% confidence interval, 1.29-5.37; P=.008). In patients with AHF, high sHSP60 was related to a higher risk for subsequent death/readmission for AHF.

Mediciones seriadas de antígeno carbohidrato 125 tras un ingreso por insuficiencia cardiaca aguda y riesgo de reingreso precoz / Carbohydrate Antigen 125 Serial Measurements after an Admission for Acute Heart Failure and Risk of Early Readmission

Fundament and objectives: The early readmission after a hospitalization for acute heart failure (AHF) is frequent; however, factors associated are not clearly established. Plasma levels of carbohydrate antigen 125 (CA125) have shown to be associated with the presence of systemic congestion and increased risk of death in patients with AHF. The aim of this study was to assess the relationship between CA125 levels (during hospitalization, at the first outpatient visit or their changes) and readmission for AHF at 6 months follow up. Patients and method: We analyzed 293 consecutive patients hospitalized for AHF in which CA125 was determined during the index hospitalization (T1) and the first outpatient visit after discharge (T2) (median 31 days). We examined the relationship between CA125 levels, both isolated determinations as their serial changes (absolute, relative or categorical) and readmission for AHF by Cox regression analysis adjusted for competing events. The reclassification technique integrated discrimination improvement (IDI) index was used to assess the additional discriminative power of this biomarker over the final multivariate model. Results: At 6 months follow up, we identified 32 (10.9%) and 54 (18.4%) deaths and readmissions for AHF, respectively. CA125 categorical changes [decrease and normalization (C1, n=153), decrease but no normalization at T2 (C2, n=72) and increase, with high levels at T2 (>35 U/ml) (C3, n=68)], followed by the isolated determination of CA125 at T2, showed the best discriminative accuracy. Thus, with respect to patients in the C1 category, patients in categories C2 and C3 showed a higher risk of readmission for AHF: C2 vs. C1: HR=3.48, 95% CI:1.84-6.59, p<0.001; C3 vs. C1: HR=3.18, 95% CI:1.62-6.21, p=0.001 (AU)

Fundamento y objetivos: El reingreso precoz tras una hospitalización por insuficiencia cardiaca aguda (ICA) es frecuente, sin embargo, los factores asociados a este no están claramente establecidos. Los valores plasmáticos del antígeno carbohidrato 125 (CA125) han mostrado asociarse con la presencia de congestión sistémica y aumento del riesgo de muerte en pacientes con ICA. El objetivo de este trabajo fue determinar la relación entre los valores de CA125 (durante el ingreso, en la primera visita ambulatoria o sus cambios) y el reingreso por ICA a 6 meses de seguimiento. Pacientes y método: Analizamos 293 pacientes consecutivos ingresados por ICA en los que se determinó el CA125 durante la hospitalización índice (T1) y en la primera visita ambulatoria (T2) tras el alta (mediana 31 días). Evaluamos la relación entre el CA125, tanto sus determinaciones aisladas como sus cambios seriados (absolutos, relativos o categóricos), y el reingreso precoz por ICA mediante análisis de regresión de Cox adaptado para episodios competitivos. La técnica de reclasificación «integrated discrimination improvement index» se utilizó para evaluar la capacidad discriminativa adicional de este biomarcador sobre el modelo multivariante final. Resultados: A 6 meses de seguimiento, se identificaron 32 (10,9%) y 54 (18,4%) muertes y reingresos por ICA, respectivamente. Los cambios categóricos de CA125 (descenso y normalización en T2 [C1, n=153], descenso pero no normalización en T2 [C2, n=72] e incremento con valores elevados en T2 [>35U/ml] [C3, n=68]), seguidos de su determinación aislada en T2, mostraron la mejor capacidad discriminativa sobre el modelo basal (AU)

Análisis mediante resonancia magnética cardiaca del miocardio salvado tras infarto. Predictores e influencia en el remodelado adverso ventricular / Analysis of post-infarction salvaged myocardium by cardiac magnetic resonance. Predictors and influence on adverse ventricular remodeling

Introducción y objetivos. Analizar mediante resonancia magnética cardiaca los factores que determinan la magnitud del miocardio salvado tras infarto de miocardio y su valor predictivo del remodelado adverso ventricular. Métodos. A 118 pacientes con un primer infarto de miocardio con elevación del ST (angioplastia primaria, 65 pacientes; estrategia farmacoinvasiva, 53 pacientes) se les realizó resonancia magnética (6 [5-8] días y 6 meses; n=83). Se cuantificó el índice de miocardio salvado como el porcentaje de área en riesgo (secuencias ponderadas en T2) que no muestra realce tardío. Resultados. El índice de miocardio salvado > 31% (mediana) se asocia a menor tiempo dolor-reperfusión (153 frente a 258 min), menor frecuencia de diabetes (el 12 frente al 32%), menor retraso hasta la resonancia magnética y mejores parámetros cardiovasculares (p<0,05 para todos ellos). No existen diferencias según el tipo de reperfusión. Mediante regresión logística, los predictores de índice de miocardio salvado > 31% son el retraso hasta la reperfusión (odds ratio = 0,42 [0,29-0,63]; p<0,0001), diabetes (odds ratio=0,32 [0,11-0,99]; p<0,05) y el retraso hasta la resonancia magnética (odds ratio=0,86 [0,76-0,97]; p<0,05). Los predictores de volumen telesistólico dilatado al sexto mes son el número de segmentos con necrosis > 50% (odds ratio=1,51 [1,21-1,90]; p<0,0001) y el volumen telesistólico en la primera semana (odds ratio=1,12 [1,06-1,18]; p<0,0001). Conclusiones. La resonancia magnética permite cuantificar el miocardio salvado tras el infarto. La rapidez en recibir el tratamiento de reperfusión constituye su principal predictor. Se debe confirmar la posible relación entre el retraso en la realización de la resonancia magnética y el miocardio salvado. El miocardio salvado no mejora el valor de la resonancia para predecir remodelado adverso (AU)

Introduction and objectives. To evaluate by cardiovascular magnetic resonance those factors related to the amount of salvaged myocardium after a myocardial infarction and its value in predicting adverse ventricular remodeling. Methods. One hundred eighteen patients admitted for a first ST elevation myocardial infarction (primary angioplasty, 65 patients; a pharmacoinvasive strategy, 53 patients) underwent magnetic resonance (6 [5-8] days and 6 months; n=83). The myocardial salvage index was quantitatively assessed as the percentage of area at risk (T2-weighted sequences) not showing late enhancement. Results. Myocardial salvage index >31% (median) was associated with a shorter time to reperfusion (153min vs 258min), a lower rate of diabetes (12% vs 32%), shorter time to magnetic resonance, and better cardiovascular parameters (P<.05 for all analyses). There were no significant differences depending on the reperfusion method. In a logistic regression analysis, delayed reperfusion (odds ratio=0.42 [0.29-0.63]; P<.0001), diabetes (odds ratio=0.32 [0.11-0.99]; P<.05) and a longer time to the performance of magnetic resonance (odds ratio=0.86 [0.76-0.97]; P<.05) were independently related to a lower probability of a myocardial salvage index >31%. Predictors of increased left ventricular end-systolic volume at 6 months were the number of segments showing an extent of transmural necrosis >50% (odds ratio =1.51 [1.21-1.90]; P<.0001) and left ventricular end-systolic volume at one week (odds ratio=1.12 [1.06-1.18]; P<.0001). Conclusions. Cardiovascular magnetic resonance enables the quantification of the salvaged myocardium after myocardial infarction. The celerity with which reperfusion therapy is administered constitutes its most important predictor. The possible effect of a delay in the performance of magnetic resonance on myocardial salvage needs to be confirmed. Salvaged myocardium does not improve the value of magnetic resonance for predicting adverse remodeling (AU)

Analysis of post-infarction salvaged myocardium by cardiac magnetic resonance. Predictors and influence on adverse ventricular remodeling.

INTRODUCTION AND OBJECTIVES: To evaluate by cardiovascular magnetic resonance those factors related to the amount of salvaged myocardium after a myocardial infarction and its value in predicting adverse ventricular remodeling. METHODS: One hundred eighteen patients admitted for a first ST elevation myocardial infarction (primary angioplasty, 65 patients; a pharmacoinvasive strategy, 53 patients) underwent magnetic resonance (6 [5-8] days and 6 months; n=83). The myocardial salvage index was quantitatively assessed as the percentage of area at risk (T2-weighted sequences) not showing late enhancement. RESULTS: Myocardial salvage index >31% (median) was associated with a shorter time to reperfusion (153 min vs 258 min), a lower rate of diabetes (12% vs 32%), shorter time to magnetic resonance, and better cardiovascular parameters (P<.05 for all analyses). There were no significant differences depending on the reperfusion method. In a logistic regression analysis, delayed reperfusion (odds ratio=0.42 [0.29-0.63]; P<.0001), diabetes (odds ratio=0.32 [0.11-0.99]; P<.05) and a longer time to the performance of magnetic resonance (odds ratio=0.86 [0.76-0.97]; P<.05) were independently related to a lower probability of a myocardial salvage index >31%. Predictors of increased left ventricular end-systolic volume at 6 months were the number of segments showing an extent of transmural necrosis >50% (odds ratio =1.51 [1.21-1.90]; P<.0001) and left ventricular end-systolic volume at one week (odds ratio=1.12 [1.06-1.18]; P<.0001). CONCLUSIONS: Cardiovascular magnetic resonance enables the quantification of the salvaged myocardium after myocardial infarction. The celerity with which reperfusion therapy is administered constitutes its most important predictor. The possible effect of a delay in the performance of magnetic resonance on myocardial salvage needs to be confirmed. Salvaged myocardium does not improve the value of magnetic resonance for predicting adverse remodeling.

Metabolomic profile of human myocardial ischemia by nuclear magnetic resonance spectroscopy of peripheral blood serum: a translational study based on transient coronary occlusion models.

OBJECTIVES: The aim of this study was to investigate the metabolomic profile of acute myocardial ischemia (MIS) using nuclear magnetic resonance spectroscopy of peripheral blood serum of swine and patients undergoing angioplasty balloon-induced transient coronary occlusion. BACKGROUND: Biochemical detection of MIS is a major challenge. The validation of novel biosignatures is of utmost importance. METHODS: High-resolution nuclear magnetic resonance spectroscopy was used to profile 32 blood serum metabolites obtained (before and after controlled ischemia) from swine (n = 9) and patients (n = 20) undergoing transitory MIS in the setting of planned coronary angioplasty. Additionally, blood serum of control patients (n = 10) was sequentially profiled. Preliminary clinical validation of the developed metabolomic biosignature was undertaken in patients with spontaneous acute chest pain (n = 30). RESULTS: Striking differences were detected in the blood profiles of swine and patients immediately after MIS. MIS induced early increases (10 min) of circulating glucose, lactate, glutamine, glycine, glycerol, phenylalanine, tyrosine, and phosphoethanolamine; decreases in choline-containing compounds and triacylglycerols; and a change in the pattern of total, esterified, and nonesterified fatty acids. Creatine increased 2 h after ischemia. Using multivariate analyses, a biosignature was developed that accurately detected patients with MIS both in the setting of angioplasty-related MIS (area under the curve 0.94) and in patients with acute chest pain (negative predictive value 95%). CONCLUSIONS: This study reports, to the authors' knowledge, the first metabolic biosignature of acute MIS developed under highly controlled coronary flow restriction. Metabolic profiling of blood plasma appears to be a promising approach for the early detection of MIS in patients.

Continuous ambulatory peritoneal dialysis as a therapeutic alternative in patients with advanced congestive heart failure.

AIMS: Continuous ambulatory peritoneal dialysis (CAPD) has been proposed as an additional therapeutic resource for patients with advanced congestive heart failure (CHF). The objective of this study was to determine the therapeutic role of CAPD, in terms of surrogate endpoints, in the management of patients with advanced CHF and renal dysfunction. METHODS AND RESULTS: A total of 57 candidates with New York Heart Association (NYHA) class III/IV CHF, renal dysfunction (glomerular filtration rate < 60 mL/min/1.73 m(2)), persistent fluid congestion despite loop diuretic treatment, and at least two previous hospitalizations for acute heart failure (AHF) were invited to be included in the CAPD programme; however, 25 patients were finally included. The primary outcome was evaluated by the change at 6 and 24 weeks for the Minnesota Living With Heart Failure Questionnaire (MLWHFQ), the 6 min walk test (6MWT), NYHA class, serum natriuretic peptides [brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP)], serum carbohydrate antigen 125 (CA125), and hospitalization rates for AHF. CAPD was associated with a substantial improvement in the MLWHFQ (-21.3, P < 0.001; and -20.4, P < 0.001), the 6MWT (54.0, P < 0.001; and 45.6, P = 0.023), and NYHA class (-1.0, P < 0.001; and -1.4, P < 0.001) at 6 and 24 weeks, respectively. The Ln(CA125) decreased markedly (-0.8, P = 0.003; and -0.98, P = 0.003), with no effect on BNP and NT-proBNP. There was a marked reduction in the number of days hospitalized for AHF (6 month post-CAPD vs. 6 months pre-CAPD: -84%; P < 0.001). CONCLUSIONS: In advanced CHF and renal dysfunction, CAPD was associated with short/mid-term improvement in severity parameters, with an acceptable rate of side effects.

Function of remote non-infarcted myocardium after STEMI: analysis with cardiovascular magnetic resonance.

To evaluate remote myocardial function after ST-elevation myocardial infarction (STEMI) and the impact of infarct size (IS) using cardiovascular magnetic resonance (CMR). 161 patients and 15 controls underwent CMR at 1st week and 6th month after STEMI. Using the 17-segments model, segments were categorized into infarcted, adjacent and remote myocardium. Relative systolic wall thickening (SWT, %) was assessed using the centerline method. IS (% of left ventricular mass) was determined in late enhancement imaging. Overall, in remote myocardium, SWT was comparable (83 ± 32) to controls (77 ± 25, P = .5) and did not increase significantly (P = .2) at the 6th month (88 ± 35, P = .3 vs. control). When IS was categorized into tertiles (<13.6%, (n = 49), 13.7-28.2%, (n = 60), >28.2%, (n = 52)), SWT in the remote area at the 1st week was not different from controls, regardless of infarct size (p between .2 and .8 for all tertiles). At 6 months, SWT was larger compared to controls only in small infarctions (98 ± 34 vs. 77 ± 25, P = .03). In medium and large infarctions there was no difference in SWT of the remote area compared to controls (87 ± 33 and 79 ± 34, P = .3 and P = .09) and there was no significant increase at 6 months (P between .2 and .9). In remote myocardium there was no difference in contractility compared to controls after STEMI. After 6 month a slight hypercontractility can only be observed in small infarctions. In medium and large infarctions no difference of SWT in remote myocardium compared to controls can be observed.

Antigen carbohydrate 125 and brain natriuretic peptide serial measurements for risk stratification following an episode of acute heart failure.

BACKGROUND: The prognostic utility of combining serial measurements of brain natriuretic peptide (BNP) and antigen carbohydrate 125 (CA125) is largely unknown. The aim of this work is to assess the prognostic utility of serial measurements of BNP, CA125, and their optimal combination for predicting long-term mortality, following a hospitalization for acute heart failure (AHF). METHODS AND RESULTS: We analyzed 293 consecutive patients admitted with AHF where CA125 and BNP were measured at discharge (T1) and at the first ambulatory visit (T2: median 31 days after discharge). Biomarkers were evaluated as snapshot determinations or as serial changes in absolute, relative or categorical changes and related to subsequent mortality with Cox regression analysis. The incremental prognostic value added by each biomarker was evaluated by the integrated discrimination improvement (IDI) index. During a median follow-up of 18 months, 91 deaths (31.1%) were identified. From the different metrics tested, the categorical changes in CA125 (Normalization: decreasing to≤35 U/ml at T2; Decreasing but not normalization: decreasing but T2>35 U/ml; small-increase: increasing but T2≤35 U/ml and; high-increase: increasing and T2>35 U/ml) showed the best discriminative accuracy. For BNP none of the serial changes metrics tested were superior to a single determination at T2 (BNP≥100 pg/ml). Adding these two biomarkers characterization to the clinical model, resulted in a 9.21% (p<0.001) gain in IDI index. CONCLUSIONS: In patients discharged for AHF, CA125 modeled as a pre-post categorical change, and BNP as a single determination at T2, resulted in the best marker combination for predicting all-cause mortality.

Differential prognostic effect of revascularization according to a simple comorbidity index in high-risk non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Data on the effect of revascularization on outcome in patients with high-risk non-ST-segment elevation acute coronary syndrome (NSTEACS) and significant comorbidities are scarce. Recently, a simple comorbidity index (SCI) including 5 comorbidities (renal failure, dementia, peripheral artery disease, heart failure, and prior myocardial infarction [MI]) has shown to be a useful tool for risk stratification. Nevertheless, therapeutic implications have not been derived. HYPOTHESIS: We sought to evaluate the prognostic effect attributable to revascularization in NSTEACS according the SCI score. METHODS: We included 1017 consecutive patients with NSTEACS. The effect of revascularization on a combined end point of all-cause mortality or nonfatal MI was evaluated by Cox regression according to SCI categories. RESULTS: A total of 560 (55.1%), 236 (23.2%), and 221 (21.7%) patients showed 0, 1, and ≥2 points according to the SCI, respectively. Coronary angiography was performed in 725 patients (71.5%), and 450 patients (44.3%) underwent revascularization. During a median follow-up of 16 months (interquartile range, 12-36 months), 305 (30%) patients experienced the combined end point (202 deaths [19.9%] and 170 MIs [16.7%]). In multivariate analysis, a differential prognostic effect of revascularization was observed comparing SCI ≥2 vs 0 (P for interaction = 0.008). Thus, revascularization was associated with a greater prognostic benefit in patients with SCI ≥2 (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.29-0.89), P = 0.018), whereas no significant benefit was observed in those with 0 and 1 point (HR: 1.31, 95% CI: 0.88-1.94, P = 0.171 and HR: 1.11, 95% CI: 0.70-1.76, P = 0.651, respectively). CONCLUSIONS: In NSTEACS, the SCI score appears to be a useful tool for identifying a subset of patients with a significant long-term death/MI risk reduction attributable to revascularization.

Prognostic implications of dipyridamole cardiac MR imaging: a prospective multicenter registry.

PURPOSE: To evaluate dipyridamole cardiac magnetic resonance (MR) imaging in the prediction of major events (MEs) in patients with ischemic chest pain in a large multicenter registry. MATERIALS AND METHODS: Institutional ethics committee approval and written informed consent were obtained. A total of 1722 patients who were undergoing cardiac MR imaging for chest pain were included. Wall motion abnormalities (WMAs) at rest, hyperemia perfusion defect (PD), late gadolinium enhancement (LGE), and inducible WMA were analyzed (abnormal if more than one abnormal segment was seen) with the 17-segment model. A cardiac MR categorization was created: category 1, no PD, LGE, or inducible WMA; category 2, PD without LGE and inducible WMA; category 3, LGE without inducible WMA; and category 4, inducible WMA. The association with ME was analyzed by using Cox proportional hazard regression multivariate models. RESULTS: During a median follow-up period of 308 days, 61 MEs (4%) occurred (36 cardiac deaths, 25 nonfatal myocardial infarctions). MEs were associated with a greater extent of WMA, PD, LGE, and inducible WMA (P ≤ .001 for all analyses). In multivariable analyses, PD (P = .002) and inducible WMA (P = .0001) were the only cardiac MR predictors. ME rate in categories 1, 2, 3, and 4 was 2% (14 of 901 patients), 3% (six of 219 patients), 4% (15 of 409 patients), and 14% (26 of 193 patients), respectively (category 4 vs category 1, adjusted P < .001). Cardiac MR-directed revascularization was performed in 242 patients (14%) and reduced the risk of ME in only category 4 (7% [six of 92 patients] vs 26% [26 of 101 patients], P = .0004). CONCLUSION: Dipyridamole cardiac MR imaging can be used to predict MEs in patients with ischemic chest pain. Patients with inducible WMA are at the highest risk for MEs and benefit the most from revascularization.

[Carbohydrate antigen 125 serial measurements after an admission for acute heart failure and risk of early readmission]. / Mediciones seriadas de antígeno carbohidrato 125 tras un ingreso por insuficiencia cardiaca aguda y riesgo de reingreso precoz.

UNLABELLED: FUNDAMENT AND OBJECTIVES: The early readmission after a hospitalization for acute heart failure (AHF) is frequent; however, factors associated are not clearly established. Plasma levels of carbohydrate antigen 125 (CA125) have shown to be associated with the presence of systemic congestion and increased risk of death in patients with AHF. The aim of this study was to assess the relationship between CA125 levels (during hospitalization, at the first outpatient visit or their changes) and readmission for AHF at 6 months follow up. PATIENTS AND METHOD: We analyzed 293 consecutive patients hospitalized for AHF in which CA125 was determined during the index hospitalization (T1) and the first outpatient visit after discharge (T2) (median 31 days). We examined the relationship between CA125 levels, both isolated determinations as their serial changes (absolute, relative or categorical) and readmission for AHF by Cox regression analysis adjusted for competing events. The reclassification technique integrated discrimination improvement (IDI) index was used to assess the additional discriminative power of this biomarker over the final multivariate model. RESULTS: At 6 months follow up, we identified 32 (10.9%) and 54 (18.4%) deaths and readmissions for AHF, respectively. CA125 categorical changes [decrease and normalization (C1, n=153), decrease but no normalization at T2 (C2, n=72) and increase, with high levels at T2 (>35 U/ml) (C3, n=68)], followed by the isolated determination of CA125 at T2, showed the best discriminative accuracy. Thus, with respect to patients in the C1 category, patients in categories C2 and C3 showed a higher risk of readmission for AHF: C2 vs. C1: HR=3.48, 95% CI:1.84-6.59, p<0.001; C3 vs. C1: HR=3.18, 95% CI:1.62-6.21, p=0.001. On the other hand, patients with elevated levels of CA125 in T2 (>35 U/ml) (41%) tripled the risk of readmission for AHF at 6 months compared with those with normal levels of CA125 at T2: HR=3.06, 95% CI:1.79-5.23, p<0.001. The addition of the categories of serial measurements of CA125 and the presence of elevated levels of CA125 at T2 showed a significant increase in the discriminating power of 6.27% and 6.17% in the IDI index, respectively. CONCLUSIONS: After an episode of AHF, the elevation of CA125 levels (>35 U/ml) after the first weeks of admission is associated with an increased risk of readmission for AHF.

Beneficios del tratamiento con estatinas según los valores plasmáticos del antígeno carbohidrato 125 tras un ingreso por insuficiencia cardiaca aguda / Benefits of statin therapy based on plasma carbohydrate antigen 125 values following an admission for acute heart failure

Introducción y objetivos. La utilidad de las estatinas en pacientes con insuficiencia cardiaca es motivo de controversia. Bajo la hipótesis de que el tratamiento con estatinas sería útil en los pacientes con insuficiencia cardiaca y mayor actividad inmunoinflamatoria, pretendimos conocer si la elevación del antígeno carbohidrato 125, un biomarcador asociado a la congestión sistémica y actividad inflamatoria, identificaría a los que se beneficiarían, en cuanto a mortalidad, del tratamiento con estatinas tras un ingreso por insuficiencia cardiaca aguda. Métodos. Analizamos a 1.222 pacientes consecutivos ingresados por insuficiencia cardiaca aguda. El antígeno carbohidrato 125 se determinó durante el ingreso hospitalario y se dicotomizó según los valores de referencia (> 35 U/ml). Resultados. Se observaron valores elevados del antígeno carbohidrato 125 en 793 pacientes (64,9%) y a 455 (37,2%) se les prescribió estatinas. Entre los pacientes con antígeno carbohidrato 125>35 U/ml, la mortalidad de los tratados con estatinas fue inferior (1,89 frente a 2,80/10 pacientes-año de seguimiento; p<0,001). Por el contrario, la mortalidad de aquellos con valores de antígeno carbohidrato 125 ≤ 35 U/ml fue similar (1,76 frente a 1,63/10 pacientes-años de seguimiento; p=0,862). Tras un minucioso ajuste multivariable, este efecto diferencial atribuible al tratamiento con estatinas persistió (para la interacción, p=0,024). Así, el tratamiento con estatinas se asoció con una reducción significativa del riesgo de muerte de los sujetos con antígeno carbohidrato 125>35 U/ml (hazard ratio=0,65; intervalo de confianza del 95%, 0,51-0,82; p<0,001); sin embargo, no fue así en aquellos con valores de antígeno carbohidrato 125 ≤ 35 U/ml (hazard ratio=1,02; intervalo de confianza del 95%, 0,74-1,41; p=0,907). Conclusiones. La elevación plasmática del antígeno carbohidrato 125 identificó un subgrupo de población que podría beneficiarse del tratamiento con estatinas en términos de mortalidad a largo plazo (AU)

Introduction and objectives. The prognostic benefit of statins in patients with heart failure is a topic of controversy. Under the hypothesis that statins may provide greater benefit in a subgroup of patients with heightened inflammatory activity, we sought to explore whether statins are associated with a decreased risk of long-term mortality in patients with acute heart failure based on elevated levels of carbohydrate antigen 125, a biomarker related to systemic congestion and proinflammatory status. Methods. We analysed 1222 consecutive patients admitted with acute heart failure in a single teaching center during a median follow-up of 20 months. Carbohydrate antigen 125 was measured during index hospitalization and dichotomized according to the established reference cut-off (>35 U/mL). Results. Increased levels of carbohydrate antigen 125 (>35 U/mL) were observed in 793 (64.9%) and prescription of statins registered in 455 (37.2%) patients. In patients with carbohydrate antigen 125 >35 U/mL, mortality was lower in statin-treated patients (1.89 vs 2.80 per 10 patient-years of follow-up, P<.001). Conversely, in those with carbohydrate antigen 125 in normal range, mortality did not differ (1.76 vs 1.63 per 10 patient-years of follow-up, P=.862). After covariate adjustment, this differential effect persisted (P for interaction=.024) and statin use was associated with a significant mortality reduction in patients with elevated values of carbohydrate antigen 125 (hazard ratio=0.65, 95% confidence interval: 0.51-0.82; P<.001), but not in those with values equal to or below 35 U/mL (hazard ratio=1.02, 95% confidence interval: 0.74-1.41; P=.907). Conclusions. Elevation of carbohydrate antigen 125 (>35 U/mL) identified a subset of patients with acute heart failure who could benefit from statin treatment in regard to total mortality (AU)

[Benefits of statin therapy based on plasma carbohydrate antigen 125 values following an admission for acute heart failure]. / Beneficios del tratamiento con estatinas según los valores plasmáticos del antígeno carbohidrato 125 tras un ingreso por insuficiencia cardiaca aguda.

INTRODUCTION AND OBJECTIVES: The prognostic benefit of statins in patients with heart failure is a topic of controversy. Under the hypothesis that statins may provide greater benefit in a subgroup of patients with heightened inflammatory activity, we sought to explore whether statins are associated with a decreased risk of long-term mortality in patients with acute heart failure based on elevated levels of carbohydrate antigen 125, a biomarker related to systemic congestion and proinflammatory status. METHODS: We analysed 1222 consecutive patients admitted with acute heart failure in a single teaching center during a median follow-up of 20 months. carbohydrate antigen 125 was measured during index hospitalization and dichotomized according to the established reference cut-off (>35 U/mL). RESULTS: Increased levels of carbohydrate antigen 125 (>35 U/mL) were observed in 793 (64.9%) and prescription of statins registered in 455 (37.2%) patients. In patients with carbohydrate antigen 125 >35 U/mL, mortality was lower in statin-treated patients (1.89 vs 2.80 per 10 patient-years of follow-up, P <.001). Conversely, in those with carbohydrate antigen 125 in normal range, mortality did not differ (1.76 vs 1.63 per 10 patient-years of follow-up, P = .862). After covariate adjustment, this differential effect persisted (P for interaction = .024) and statin use was associated with a significant mortality reduction in patients with elevated values of carbohydrate antigen 125 (hazard ratio=0.65, 95% confidence interval: 0.51-0.82; P <.001), but not in those with values equal to or below 35 U/mL (hazard ratio=1.02, 95% confidence interval: 0.74-1.41; P = .907). CONCLUSIONS: Elevation of carbohydrate antigen 125 (>35 U/mL) identified a subset of patients with acute heart failure who could benefit from statin treatment in regard to total mortality.

Prognostic implications of arterial blood gases in acute decompensated heart failure.

BACKGROUND: The prognostic value of arterial blood gases (ABG) in patients with acute decompensated heart failure (ADHF) is not well-established. We therefore conducted the present study to determine the relationship between ABG on admission and long-term mortality in patients with ADHF. METHODS: We studied 588 patients consecutively admitted to our department with ADHF. ABG and classical prognostic variables were determined at patients' arrival to the emergency department. The independent association among the main variables of ABG (pO2, pCO2 and pH) and mortality was assessed with Cox regression analysis. RESULTS: At a median follow-up of 23months, 221 deaths (37.6%) were registered. 308 (52.4%), 54 (9.2%) and 50 (8.5%) patients showed hypoxemia (pO2<60mmHg), hypercapnia (pCO2>50mmHg) and acidosis (pH<7.35), respectively. Patients with hypoxemia, hypercapnia and acidosis did not show higher mortality rates (38% vs. 37.1%, 42.6% vs. 37.1%, and 48% vs. 36.6%, respectively; p-value=ns for all comparisons). In multivariate analysis, after adjusting for well-known prognostic covariates, pO2, pCO2 and pH did not show a significant association with mortality. Hazard ratios (HR) for these variables were: pO2, per increase in 10mmHg: 0.99 (95% CI: 0.90-1.09), p=0.861; pCO2, per increase in 10mmHg: 1.12 (95% CI: 0.91-1.39), p=0.262; pH per increase in 0.1: 1.01 (95% CI: 0.99-1.04), p=0.309. When dichotomizing these variables according to established cut-points, the HR were: hypoxemia (pO2<60mmHg):1.07 (95% CI: 0.81-1.40), p=0.637; hypercapnia (pCO2>50mmHg): 0.98 (95% CI: 0.62-1.57), p=0.952; acidosis (pH<7.35): 1.38 (95% CI: 0.87-2.19), p=0.173. CONCLUSION: In patients admitted with ADHF, admission arterial pO2, pCO2 and pH were not associated with all-cause long-term mortality.

Effectiveness of the relative lymphocyte count to predict one-year mortality in patients with acute heart failure.

Several works have endorsed a significant role of the immune system and inflammation in the pathogenesis of heart failure. As indirect evidence, an association between a low relative lymphocyte count (RLC%) and worse outcomes found in this population has been suggested. Nevertheless, the role of RLC% for risk stratification in a large and nonselected population of patients with acute heart failure (AHF) has not yet been determined. Thus, the aim of this study was to determine the association between low RLC% and 1-year mortality in patients with AHF and consequently to define whether it has any role for early risk stratification. A total of 1,192 consecutive patients admitted for AHF were analyzed. Total white blood cell and differential counts were measured on admission. RLC% (calculated as absolute lymphocyte count/total white blood cell count) was categorized in quintiles and its association with all-cause mortality at 1 year assessed using Cox regression. At 1 year, 286 deaths (24%) were identified. A negative trend was observed between 1-year mortality rates and quintiles of RLC%: 31.5%, 27.2%, 23.1%, 23%, and 15.5% in quintiles 1 to 5, respectively (p for trend <0.001). After thorough covariate adjustment, only patients in the lowest quintile (<9.7%) showed an increased risk for mortality (hazard ratio 1.76, 95% confidence interval 1.17 to 2.65, p = 0.006). When RLC% was modeled with restricted cubic splines, a stepped increase in risk was observed patients in quintile 1: those with RLC% values <7.5% and <5% showed 1.95- and 2.66-fold increased risk for death compared to those in the top quintile. In conclusion, in patients with AHF, RLC% is a simple, widely available, and inexpensive biomarker, with potential for identifying patients at increased risk for 1-year mortality.