Red blood cell distribution width is longitudinally associated with mortality and anemia in heart failure patients.

BACKGROUND: Red blood cell distribution width (RDW) has been found to be an independent predictor for adverse outcome in patients with heart failure (HF), but there are no data on the association of longitudinal RDW with all-cause mortality and occurrence of anemia. METHODS AND RESULTS: 1,702 patients discharged from a previous admission for acute HF (AHF) were included. RDW was measured during the available longitudinal history of the patient. Joint modeling and Multistate Markov were used for the analysis. The median RDW at baseline was 15.0% (IQR: 14.0-16.5), and 45.6% of patients had anemia. At a median follow-up of 1.5 years (IQR: 0.45-3.25), 713 patients died. The last RDW-trajectory value and cumulative RDW-trajectory mean were predictive of mortality (HR, 1.18; 95% CI: 1.12-1.24; and HR, 1.12; 95% CI: 1.08-1.16, respectively; P<0.001 for both). This effect, however, varied according the anemia status (P for interaction<0.001), being more pronounced in absence of anemia [HR=1.31 (95% CI: 1.22-1.42) and HR=1.48 (95% CI: 1.33-1.64)] compared to those with anemia [HR=1.08 (95% CI: 1.04-1.13), 1.12 (95% CI: 1.06-1.18)]. Longitudinal RDW (per 1% increasing) was also independently associated with incident anemia [HR=1.10 (95% CI: 1.03-1.18) P=0.002]. CONCLUSIONS: Following an admission for AHF, higher longitudinal RDW values over time were associated to an increased risk for both developing anemia and dying. The effect on mortality was more pronounced among non-anemic patients.

Outcome of patients with syncope beyond the implantable loop recorder.

AIMS: The implantation of an implantable loop recorder (ILR) leads to the diagnosis in about 35% of patients with syncope of unknown origin. Information on outcome of patients in whom a diagnosis is not reached during the lifetime of the device is scarce. The aim of our study is to determine the outcome of these patients in terms of syncope recurrence and survival. METHODS AND RESULTS: An ILR was implanted to 97 patients with syncope of unknown origin. Patients were classified in groups A and B depending on their high or low risk, respectively, of having arrhythmic syncope. Diagnosis had not been reached in 60 patients (62%) when the ILR battery reached end operational life. Five patients were lost to follow up. During a median follow-up of 48 months after ILR explantation (interquartile range 36-56), 22 patients (40%) had recurrence of syncope (32% in group A vs. 48% in group B, P = 0.3). Syncopes with no neurally mediated profile were more frequent in group A (18 vs. 0%, P = 0.05) and neurally mediated profile syncopes were more frequent in group B (44 vs. 11%, P = 0.007). Five patients died, four of them in group A and 1 in group B (P = 0.4). No sudden or cardiac deaths were detected during follow-up. All deaths were due to non-cardiac causes. CONCLUSION: Recurrent syncope is common in patients in whom a diagnosis is not established after the full battery life of an ILR. The prognosis of these patients seems to be good, without observed sudden or cardiac death.

Usefulness of pain presentation characteristics for predicting outcome in patients presenting to the hospital with chest pain of uncertain origin.

BACKGROUND: Decision making in chest pain of uncertain origin is challenging. OBJECTIVES: To evaluate the predictive value of simple characteristics of pain presentation in patients coming to the emergency department with chest pain and without electrocardiogram ischaemia or raised troponin. METHODS: 789 patients were studied. The following categorical pain characteristics were collected: effort related pain, pressing character, radiation, associated symptoms, and ≥ 2 episodes in 24 h. Additionally, a predefined semi-quantitative pain score including seven items (Geleijnse score) was completed. Risk factors and co-morbidities were also recorded. The primary and secondary endpoints were cardiac events at 30 days and at 1 year. RESULTS: After adjusting for risk factors and co-morbidites, the pain characteristics associated with the primary and secondary endpoints were effort related pain (HR=2.1, 95% CI 1.5 to 3.0, p=0.0001; HR=1.8, 95% CI 1.3 to 2.5, p=0.0003) and ≥ 2 episodes in 24 h (HR=2.4, 95% CI 1.7 to 3.5, p=0.0001; HR=2.3, 95% CI 1.7 to 3.2, p=0.0001). Both variables retained their predictive value in women, diabetics and elderly (>70 years) patients. The discriminatory capacity of the predictive models including these two pain characteristics for the primary and secondary endpoints (C-statistic 0.76 and 0.76) was better than using the complex semi-quantitative pain score (C-statistic 0.69 and 0.71). CONCLUSION: In patients presenting to the emergency department with chest pain and without electrocardiogram ischaemia or raised troponin, effort related pain and ≥ 2 episodes in 24 h are the main characteristics to be considered for decision making.

Vasodilator Stress CMR and All-Cause Mortality in Stable Ischemic Heart Disease: A Large Retrospective Registry.

OBJECTIVES: This study explored the association of ischemic burden, as measured by vasodilator stress cardiovascular magnetic resonance (CMR), with all-cause mortality and the effect of revascularization on all-cause mortality in patients with stable ischemic heart disease (SIHD). BACKGROUND: In patients with SIHD, the association of ischemic burden, derived from vasodilator stress CMR, with all-cause mortality and its role for decision-making is unclear. METHODS: The registry consisted of 6,389 consecutive patients (mean age: 65 ± 12 years; 38% women) who underwent vasodilator stress CMR for known or suspected SIHD. The ischemic burden (at stress first-pass perfusion imaging) was computed (17-segment model). The effect of CMR-related revascularization (within the following 3 months) on all-cause mortality was retrospectively explored using the electronic regional health system registry. RESULTS: During a 5.75-year median follow-up, 717 (11%) deaths were documented. In multivariable analyses, more extensive ischemic burden (per 1-segment increase) was independently related to all-cause mortality (hazard ratio: 1.04; 95% confidence interval: 1.02 to 1.07; p < 0.001). In 1,032 1:1 matched patients using a limited number of variables (516 revascularized, 516 non-revascularized), revascularization within the following 3 months was associated with less all-cause mortality only in patients with extensive CMR-related ischemia (>5 segments, n = 432; 10% vs. 24%; p = 0.01). CONCLUSIONS: In a large retrospective registry of unselected patients with known or suspected SIHD who underwent vasodilator stress CMR, extensive ischemic burden was related to a higher risk of long-term, all-cause mortality. Revascularization was associated with a protective effect only in the restricted subset of patients with extensive CMR-related ischemia. Further research will be needed to confirm this hypothesis-generating finding.

Usefulness of the neutrophil to lymphocyte ratio in predicting long-term mortality in ST segment elevation myocardial infarction.

Neutrophil to lymphocyte ratio (N/L) has been associated with poor outcomes in patients who underwent cardiac angiography. Nevertheless, its role for risk stratification in acute coronary syndromes, specifically in patients with ST-segment elevation myocardial infarction (STEMI), has not been elucidated. We sought to determine the association of N/L maximum value (N/L max) with mortality in the setting of STEMI and to compare its predictive ability with total white blood cell maximum count (WBC max). We analyzed 515 consecutive patients admitted with STEMI to a single university center. White blood cells (WBC) and differential count were measured at admission and daily for the first 96 hours afterward. Patients with cancer, inflammatory diseases, or premature death were excluded, and 470 patients were included in the final analysis. The association between N/L max and WBC max with mortality was assessed by Cox regression analysis. During follow-up, we registered 106 deaths (22.6%). A positive trend between mortality and N/L max quintiles was observed; 6.4%, 12.4%, 11.7%, 34%, and 47.9% of deaths occurred from quintiles 1 to 5 (p <0.001), respectively. In a multivariable setting, after adjusting for standard risk factors, patients in the fourth (Q4 vs Q1) and fifth quintile (Q5 vs Q1) showed the highest mortality risk (hazard ratio 2.58, 95% confidence interal 1.06 to 6.32, p = 0.038 and hazard ratio 4.20, 95% confidence interal 1.73 to 10.21, p = 0.001, respectively). When WBC max and cells subtypes were entered together, N/L max remained as the only WBC parameter; furthermore, the model with N/L max showed the most discriminative ability. In conclusion, N/L max is a useful marker to predict subsequent mortality in patients admitted for STEMI, with a superior discriminative ability than total WBC max.

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).

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.

Echocardiographic estimation of pulmonary arterial systolic pressure in acute heart failure. Prognostic implications.

BACKGROUND: Prognostic implications of echocardiographic assessment of pulmonary hypertension (PH) in non-selected patients hospitalized for acute heart failure (AHF) are not clearly defined. The aim of this study was to evaluate the association between echocardiography-derived PH in AHF and 1-year all-cause mortality. METHODS: We prospectively included 1210 consecutive patients admitted for AHF. Patients with significant heart valve disease were excluded. Pulmonary arterial systolic pressure (PASP) was estimated using transthoracic echocardiography during hospitalization (mean time after admission 96±24h). Patients were categorized as follows: non-measurable, normal PASP (PASP≤35mmHg), mild (PASP 36-45mmHg), moderate (PASP 46-60mmHg) and severe PH (PASP >60mmHg). The independent association between PASP and 1-year mortality was assessed with Cox regression analysis. RESULTS: At 1-year follow-up, 232 (19.2%) deaths were registered. PASP was measured in 502 (41.6%) patients with a median of 46 [38-55] mmHg. The distribution of population was: 708 (58.5%), 76 (6.3%), 147 (12.1%), 190 (15.7%) and 89 (7.4%) for non-measurable, normal PASP, mild, moderate and severe PH, respectively. One-year mortality was lower for patients with normal PASP (1.32 per 10 person-years), intermediate for patients with non-measurable, mild and moderate PH (2.48, 2.46 and 2.62 per 10 persons-year, respectively) and higher for those with severe PH (4.89 per 10 person-years). After multivariate adjustment, only patients with PASP >60mmHg displayed significant adjusted increase in the risk of 1-year all-cause mortality, compared to patients with normal PASP (HR=2.56; CI 95%: 1.05-6.22, p=0.038). CONCLUSIONS: In AHF, severe pulmonary hypertension derived by echocardiography is an independent predictor of 1-year-mortality.

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.

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.

Differential mortality association of loop diuretic dosage according to blood urea nitrogen and carbohydrate antigen 125 following a hospitalization for acute heart failure.

AIMS: Recent observations in chronic stable heart failure suggest that high-dose loop diuretics (HDLDs) have detrimental prognostic effects in patients with high blood urea nitrogen (BUN), but recent findings have also indicated that diuretics may improve renal function. Carbohydrate antigen 125 (CA125) has been shown to be a surrogate of systemic congestion. We sought to explore whether BUN and CA125 modulate the mortality risk associated with HDLDs following a hospitalization for acute heart failure (AHF). METHODS AND RESULTS: We analysed 1389 consecutive patients discharged for AHF. CA125 and BUN were measured at a mean of 72 ± 12 h after admission. HDLDs (≥120 mg/day in furosemide equivalent dose) were interacted to a four-level variable according to CA125 (>35 U/mL) and BUN (above the median), and related to all-cause mortality. At a median follow-up of 21 months, 561 (40.4%) patients died. The use of HDLDs was independently associated with increased mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.01-1.50], but this association was not homogeneous across CA125-BUN categories (P for interaction <0.001). In patients with normal CA125, use of HDLDs was associated with high mortality if BUN was above the median (HR 2.29, 95% 1.51-3.46), but not in those with BUN below the median (HR 1.22, 95% CI 0.73-2.04). Conversely, in patients with high CA125, HDLDs showed an association with increased survival if BUN was above the median (HR 0.73, 95% CI 0.55-0.98) but was associated with increased mortality in those with BUN below the median (HR 1.94, 95% CI 1.36-2.76). CONCLUSION: The risk associated with HDLDs in patients after hospitalization for AHF was dependent on the levels of BUN and CA125. The information provided by these two biomarkers may be helpful in tailoring the dose of loop diuretics at discharge for AHF.

Continuous ambulatory peritoneal dialysis and clinical outcomes in patients with refractory congestive heart failure.

INTRODUCTION AND OBJECTIVES: Peritoneal dialysis has been proposed as a therapeutic alternative for patients with refractory congestive heart failure. The objective of this study was to assess its effect on long-term clinical outcomes in patients with advanced heart failure and renal dysfunction. METHODS: A total of 62 patients with advanced heart failure (class III/IV), renal dysfunction (glomerular filtration<60 mL/min/1.73 m(2)), persistent fluid congestion despite loop diuretic treatment and at least 2 previous hospitalizations for heart failure were invited to participate in a continuous ambulatory peritoneal dialysis program. Of these, 34 patients were excluded and adjudicated as controls. The most important reasons for exclusion were refusal to participate, inability to perform the technique and abdominal wall defects. The primary endpoint was all-cause mortality and the composite of death/readmission for heart failure. To account for baseline imbalance, a propensity score was estimated and used as a weight in all analyses. RESULTS: The peritoneal dialysis (n=28) and control groups (n=34) were alike in all baseline covariates. During a median follow-up of 16 months, 39 (62.9%) died, 21 (33.9%) patients were rehospitalization for heart failure, and 42 (67.8%) experienced the composite endpoint. In the propensity score-adjusted models, peritoneal dialysis (vs control group) was associated with a substantial reduction in the risk of mortality using complete follow-up (hazard ratio=0.40; 95% confidence interval, 0.21-0.75; P=.005), mortality using days alive and out of hospital (hazard ratio=0.39; 95% confidence interval, 0.21-0.74; P=.004) and the composite endpoint (hazard ratio=0.32; 95% confidence interval, 0.17-0.61; P=.001). CONCLUSIONS: In refractory congestive heart failure with concomitant renal dysfunction, peritoneal dialysis was associated with long-term improvement in clinical outcomes. Full English text available from:www.revespcardiol.org.

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.

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.

One-week and 6-month cardiovascular magnetic resonance outcome of the pharmacoinvasive strategy and primary angioplasty for the reperfusion of ST-segment elevation myocardial infarction.

INTRODUCTION AND OBJECTIVES: Pharmacoinvasive strategy represents an attractive alternative to primary angioplasty. Using cardiovascular magnetic resonance imaging we compared the left ventricular outcome of the pharmacoinvasive strategy and primary angioplasty for the reperfusion of ST-segment elevation myocardial infarction. METHODS: Cardiovascular magnetic resonance was performed 1 week and 6 months after infarction in two consecutive cohorts of patients included in a prospective university hospital ST-segment elevation myocardial infarction registry. During the period 2004-2006, 151 patients were treated with pharmacoinvasive strategy (thrombolysis followed by routine non-immediate angioplasty). During the period 2007-2008, 93 patients were treated with primary angioplasty. A propensity score matched population was also evaluated. RESULTS: At 1-week cardiovascular magnetic resonance, pharmacoinvasive strategy and primary angioplasty patients showed a similar extent of area at risk (29±15 vs. 29±17%, P=.9). Non-significant differences were detected by cardiovascular magnetic resonance at 1 week and at 6 months in infarct size, salvaged myocardium, microvascular obstruction, ejection fraction, end-diastolic volume index and end-systolic volume index (P>.2 in all cases). The same trend was observed in 1-to-1 propensity score matched patients. The rate of major adverse cardiac events (death and/or re-infarction) at 1 year was 6% in pharmacoinvasive strategy and 7% in primary angioplasty patients (P=.7). CONCLUSIONS: A pharmacoinvasive strategy including thrombolysis and routine non-immediate angioplasty represents a widely available and logistically attractive approach that yields identical short-term and long-term cardiovascular magnetic resonance-derived left ventricular outcome compared to primary angioplasty.

Effect of acute heart failure following discharge in patients with non-ST-elevation acute coronary syndrome on the subsequent risk of death or acute myocardial infarction.

INTRODUCTION AND OBJECTIVES: Little is known about how prognosis is influenced by readmission for acute heart failure (AHF) following non-ST-segment elevation acute coronary syndrome (NSTEACS). The aim of this study was to determine the prognostic effect of a first admission for AHF on the risk of acute myocardial infarction (AMI) or death in patients who survived an episode of high-risk NSTEACS. METHODS: The study involved 972 consecutive patients with high-risk NSTEACS who survived after hospital admission. Readmission for AHF was selected as the main exposure variable, and its association with subsequent AMI or all-cause death was assessed using Cox proportional hazards models for time-dependent covariates that also included adjustment for competing risks. RESULTS: After a median follow-up period of 30 [interquartile range, 12-48] months, 82 patients (8.4%) were admitted for AHF, 146 (15%) had an AMI, and 202 (20.8%) died. The median time to readmission for AHF was 203 [56-336] days after NSTEACS. Patients readmitted for AHF had an increased risk of subsequent death (hazard ratio [HR]=1.67; 95% confidence interval [CI], 1.13-2.45; P=.009) or AMI (HR=2.15; 95% CI, 1.41-3.27; P< .001), which was independent of baseline prognostic and time-dependent variables. CONCLUSIONS: Readmission for AHF after high-risk NSTEACS was associated with an increased risk of subsequent death or AMI.

Effect of invasive treatment on prognosis in non-ST-segment elevation acute coronary syndrome with or without systolic dysfunction.

INTRODUCTION AND OBJECTIVES: Few data are available on the use of invasive treatment in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) and systolic dysfunction. The aim of this study was to determine the effect of invasive treatment on the prognosis of patients with NSTEACS, with or without systolic dysfunction. METHODS: The study included 972 consecutive patients admitted for NSTEACS (i.e. ST-segment depression or an elevated troponin-I level). Systolic dysfunction was defined as an ejection fraction <50% on transthoracic echocardiography. The primary long-term endpoint was death or myocardial infarction. The effect of invasive treatment on prognosis was evaluated by Cox regression analysis. RESULTS: Overall, 23.4% of patients had systolic dysfunction, and 303 (31.2%) reached the primary endpoint, which was more frequent in those with systolic dysfunction (49.8% vs. 25.5%; P< .001). Usage of coronary angiography and revascularization procedures were similar in patients with systolic dysfunction and those with an ejection fraction >/=50% (59% vs. 63.4%; P=.239; and 38.3% vs. 38.8%; P=.9; respectively). Detailed adjusted multivariate analysis, including the use of a propensity score, demonstrated that coronary angiography had a differential effect on prognosis depending on the presence or absence of systolic dysfunction (interaction, P=.01). Catheterization was clearly beneficial in patients with systolic dysfunction (hazard ratio [HR]=0.47; 95% confidence interval [CI], 0.3-0.75; P=.001) but not in those with an ejection fraction >/=50% (HR=0.9; 95% CI, 0.63-1.29; P=.567). CONCLUSIONS: The presence of systolic dysfunction identifies those patients with NSTEACS who will benefit most from invasive treatment.

Low lymphocyte count in acute phase of ST-segment elevation myocardial infarction predicts long-term recurrent myocardial infarction.

OBJECTIVE: We sought to determine the relationship between the lowest lymphocyte count (lymphocyte(min))obtained within the first 96 h of symptoms onset and the risk of postdischarge recurrent spontaneous myocardial infarction (re-MI) in patients admitted with ST-segment elevation MI (STEMI). METHODS: We analyzed 549 consecutive patients admitted with STEMI from a single academic hospital. Lymphocyte counts were determined at admission and routinely during the first 96 h. Lymphocyte(min) was selected as the main exposure. Patients with inflammatory or infectious diseases, in-hospital death, or reinfarction were excluded from the analysis (final sample= 426 patients). Lymphocyte(min) was divided into quartiles (Q) and their association with re-MI was assessed by competing risk analysis. Postdischarge death and coronary revascularization were considered competing events. RESULTS: During a median follow-up of 36 months, 53 re-MI (12.4%) were registered. The re-MI crude rate was significantly higher in patients in the lowest lymphocyte(min) quartile (Q1r1045 cells/ml) compared with Q2-Q4: 22.4, 9.4, 8.4, 9.4%, respectively; P =0.005. In a multivariate setting, Q1 was also associated with a significant increased risk of re-MI compared with Q2-Q4 (hazard ratio: 2.04, 95% confidence interval: 1.11-3.76; P = 0.021). CONCLUSION: Low lymphocyte count obtained within the first 96 h of a STEMI predicts the risk of re-MI.

Head to head comparison of quantitative versus visual analysis of contrast CMR in the setting of myocardial stunning after STEMI: implications on late systolic function and patient outcome.

To compare a quantitative assessment of contrast cardiovascular magnetic resonance (CMR) after ST-segment elevation myocardial infarction (STEMI) with visual analysis for predicting depressed ejection fraction (dEF) and major adverse cardiac events (MACE). 192 patients underwent CMR at 1 week and 6 months after STEMI. Three quantitative (initial slope, maximal signal intensity and contrast delay in first-pass imaging) and 2 visual perfusion indexes (hypoenhancement in first-pass and microvascular obstruction in late enhancement imaging (LE)) were determined. Quantification of infarct mass and visual assessment of the extent of transmural necrosis (ETN) were also performed. At 6 months, 69 patients displayed dEF. During follow-up (mean 655 days) 20 MACE (death, re-infarction, re-admission for heart failure) occurred. Perfusion quantification took longer (P < 0.001) and, in ROC curve analyses and the C-statistic, was not superior to visual perfusion analysis for predicting late EF or MACE (P = ns). Similarly, infarct size quantification was not superior to visual assessment of ETN (P = ns). In multivariate analyses, only visual assessment of ETN (per segment) predicted dEF (OR 1.30 95%CI [1.04-1.61], P = 0.02) and MACE (HR 1.38 95%CI [1.19-1.60], P < 0.001). Visual analysis of CMR after STEMI is not time consuming and predicts dEF and MACE comparable to quantification. ETN was the strongest parameter.