Incidence and predictors of new-onset atrial fibrillation in noncardiac intensive care unit patients.

BACKGROUND: Atrial fibrillation (AF) is thought to be a relatively common arrhythmia in the setting of noncardiac intensive care unit (ICU). However, data concerning AF deriving from such populations are scarce. In addition, it is unclear which of the wide spectrum of AF predictors are relevant to the ICU setting. OBJECTIVES: The aim of our study was to evaluate the incidence of new-onset AF and investigate the factors that contribute to its occurrence in ICU patients. METHODS: We prospectively studied all patients admitted to our ICU during a 1-year period. Patients admitted for brief postoperative monitoring and patients with chronic or intermittent AF and AF present upon admission were excluded. A number of conditions incriminated as AF risk factors or "triggers" from demographics, medical history, present disease, and cardiac echocardiography as well as circumstances of AF onset were recorded. RESULTS: The study population consisted of 133 patients (90 males). Atrial fibrillation was observed in 15% of them. Age older than 65 years (P=.001), arterial hypertension (P=.03), systemic inflammatory response syndrome (P<.001), sepsis (P=.001), left atrial dilatation (P=.01), and diastolic dysfunction (P=.04) were significantly associated with the occurrence of AF. By multivariate analysis, it was demonstrated that only older than 65 years (odds ratio, 7.0; 95% confidence interval, 2.0-24.6; P=.003) and sepsis (odds ratio, 6.5; 95% confidence interval, 2.0-21.1; P=.002) independently predict new-onset AF. Patients manifesting AF were frequently hypovolemic (30%) and had electrolyte disorders (40%) as well as elevated and rising serum C-reactive protein (70%). CONCLUSION: A significant fraction of ICU patients manifest AF. The predictors of interest for the ICU patients might be considerably different than those of the general population and other subgroups with systemic inflammation possibly having a pivotal role.

Prognostic usefulness of serial C-reactive protein measurements in ST-elevation acute myocardial infarction.

It has been reported that increased levels of C-reactive protein are related to adverse long-term prognosis in the setting of ST-segment elevation acute myocardial infarction (MI). In previous studies, the timing of C-reactive protein determination has varied widely. In the present study, serial high-sensitivity C-reactive protein (hsCRP) measurements were performed to investigate if any of the measurements is superior regarding long-term prognosis. A total of 861 consecutive patients admitted for ST-segment elevation MI and treated with intravenous thrombolysis within the first 6 hours from the index pain were included. HsCRP levels were determined at presentation and at 24, 48, and 72 hours. The median follow-up time was 3.5 years. New nonfatal MI and cardiac death were the study end points. By the end of follow-up, cardiac death was observed in 22.4% and nonfatal MI in 16.1% of the patients. HsCRP levels were found to be increasing during the first 72 hours. Multivariate Cox regression analysis demonstrated that hsCRP levels at presentation were an independent predictor of the 2 end points (relative risk [RR] 2.8, p = 0.002, and RR 2.1, p = 0.03, for MI and cardiac death, respectively), while hsCRP levels at 24 hours did not yield statistically significant results (RR 1.4, p = 0.40, and RR 1.1, p = 0.80, for MI and cardiac death, respectively). The corresponding RRs at 48 hours were 1.2 (p = 0.5) for MI and 3.2 (p = 0.007) for cardiac death and at 72 hours were 1.6 (p = 0.30) for MI and 3.9 (p <0.001) for cardiac death. In conclusion, hsCRP levels at presentation represent an independent predictor for fatal and nonfatal events during long-term follow-up. HsCRP levels at 48 and 72 hours, which are close to peak hsCRP levels, independently predict only cardiac death.

Plasma asymmetric dimethylarginine and mortality in patients with acute decompensation of chronic heart failure.

OBJECTIVES: To investigate the prognostic value of circulating levels of asymmetric dimethylarginine (ADMA) in patients with acute decompensation of (New York Heart Association (NYHA) class III/IV) chronic heart failure and reduced left ventricular ejection fraction. DESIGN: Single-centre prospective observational study. SETTING: Tertiary referral centre. PATIENTS: A total of 651 consecutive and eligible hospitalised patients were studied. Patients were divided into four groups according to the quartiles of circulating levels of ADMA upon presentation. MAIN OUTCOME MEASURES: Incidence of in-hospital (or 7-day in the case of prolonged hospitalisation), 31-day and 1-year cardiac mortality were the pre-specified study end points. RESULTS: Cumulative rates of in-hospital, 31-day and 1-year cardiac mortality were 10.6%, 18.7% and 36.4%, respectively. There was a gradual increased risk of in-hospital (p(for trend)=0.011), 31-day (p(for trend)=0.044) and 1-year (p(for trend)<0.001) mortality with increasing ADMA quartiles. After adjustment for possible confounders, patients at the highest ADMA quartile were at significantly higher risk for in-hospital (p=0.042), 31-day (p=0.032) and 1-year (p<0.001) mortality than those in the lowest quartile. CONCLUSIONS: According to the present results, an elevated circulating level of ADMA is a strong independent predictor of short-term and long-term mortality in patients with acute decompensation of NYHA class III/IV chronic heart failure and reduced left ventricular ejection fraction. ADMA levels upon presentation may confer enhanced risk stratification in this setting.

Anemia and early mortality in patients with decompensation of chronic heart failure.

OBJECTIVES: The possible independent effect of mild-to-moderate anemia (hemoglobin value not <9 g/dl) on the short-term mortality of patients with decompensation of NYHA class III/IV chronic heart failure has not been investigated yet. METHODS: A total of 725 consecutive hospitalized patients were studied. All-cause mortalities during hospitalization and by day 31 were the prespecified study end points. RESULTS: A total of 76 (10.5%) and 133 (18.3%) patients died during hospital stay and by day 31 of follow-up, respectively. Patients in the first hemoglobin tertile were at a significantly higher risk of death than those in the second (p = 0.003 and p < 0.001 for unadjusted in-hospital and 31-day mortality, respectively) or third terile (p < 0.001 and p < 0.001, for unadjusted in-hospital and 31-day mortality, respectively). However, after adjustment for concomitant baseline comorbidities and biochemical parameters, there was no significant difference in the risk of death among hemoglobin tertiles. CONCLUSIONS: Mild-to-moderate anemia seems not to contribute independently to short-term mortality in patients with decompensation of NYHA class III/IV chronic heart failure. An adverse concomitant baseline risk profile may have a key role in the induction of mild-to-moderate anemia and in the increased risk of death in these patients.

The impact of treatment with omeprazole on the effectiveness of clopidogrel drug therapy during the first year after successful coronary stenting.

BACKGROUND: Because clopidogrel is converted to its active metabolite by P450 isoenzymes, which are also involved in the metabolism of omeprazole, there is concern regarding whether the action of clopidogrel would be reduced in patients also taking omeprazole. OBJECTIVE: To evaluate the impact of omeprazole administration on the effectiveness of clopidogrel drug therapy during the first year following successful coronary stenting (CS). METHODS: A total of 588 consecutive patients who underwent successful CS for stable or unstable coronary artery disease were studied. Patients were classified into those who were treated (group A, n=340) or not treated (group B, n=248) with omeprazole for seven or more consecutive days during the entire observation period. The composite of cardiac death or rehospitalization for nonfatal myocardial infarction during the first year was the prespecified primary study end point. RESULTS: Baseline characteristics, and dual clopidogrel and acetylsalicylic acid drug therapy were well balanced between the study groups. By one year, the primary end point was reached by 58 (9.9%) patients, including 20 (3.4%) who died due to cardiac reasons and 38 (6.5%) who were rehospitalized because of a nonfatal myocardial infarction. Patients in groups A and B, respectively, were at similar risk of the primary composite end point (10% versus 9.7%, hazard ratio 1.1 [95% CI 0.6 to 1.8]; P=0.89). CONCLUSIONS: According to the results of the present study, treatment with omeprazole had no impact on the clinical efficacy of clopidogrel drug therapy during the first year after successful CS.

The impact of right ventricular involvement on the postdischarge long-term mortality in patients with acute inferior ST-segment elevation myocardial infarction.

OBJECTIVES: To investigate the long-term impact of right ventricular myocardial involvement (RVI) after acute inferior ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 1208 consecutive patients, who survived to discharge after hospitalization for acute inferior STEMI, were studied. Patients were divided into those with (n = 459) or without (n = 749) of RVI involvement, defined as ST-segment elevation > or =1 mm in V4R. Cardiac death by 3 years was the primary study end point. RESULTS: By the end of follow-up, 207 (17.1%) patients had died. Patients with RVI were at similar risk for death at 3 years than those without (17.6% vs 16.8%, hazard ratio 1.1, 95% confidence interval 0.8-1.4, P = .79). By multivariate Cox analysis, several variables, but not RVI, were associated with the incidence of 3 years cardiac death. CONCLUSIONS: Right ventricular myocardial involvement does not portend any increased risk for long-term mortality, in patients who survived to discharge after hospitalization for acute inferior STEMI.

Multimarker strategy for the prediction of 31 days cardiac death in patients with acutely decompensated chronic heart failure.

BACKGROUND: To investigate the combined prognostic value of admission serum levels of B-type natriuretic peptide (BNP), cardiac troponin I (cTnI) and high sensitivity C-reactive protein (hs-CRP), in patients hospitalized because of acutely decompensated severe (New York Heart Association class III/IV) low-output chronic heart failure (CHF). METHODS: A total of 577 consecutive patients recruited in the 5 participating centers, were studied. Cardiac mortality by 31 days was the prespecified primary study end point. RESULTS: A total of 102 (17.7%) patients died by 31 days. When the study patients were divided according to the number of elevated study biomarkers, there was a significant gradual increased risk of 31-day cardiac death with increasing in the number of elevated biomarkers (p<0.001). The value of the discriminant C statistic for the Cox regression analysis, increased significantly when each of the study biomarkers was incorporated with the other risk predictors into a Cox regression model, with the highest C statistic value for the Cox regression model that included all the study biomarkers (p<0.001). By multivariate Cox regression analysis, elevated serum levels of BNP (p=0.002), cTnI (p<0.001) and hs-CRP (p=0.02) were independent predictors of the study end point. CONCLUSIONS: In conclusion, in patients hospitalized for acute decompensation of severe (NYHA III/IV) low-output CHF, BNP, cTnI and hs-CRP upon admission offers enhanced early risk stratification. With increasing number of elevated biomarkers, the risk of 31-day cardiac death increases gradually that implies treatment intensification, and closer follow-up.

The effect of open-chest cardiac resuscitation on mitral regurgitant flow: an on-line transesophageal echocardiographic study in dogs.

INTRODUCTION: We sought to determine the effect of cardiac massage on a pre-existing regurgitant mitral valve during open-chest cardiopulmonary resuscitation (OCCPR) in an animal experiment. METHODS: Our study included 29 dogs that were used as experimental models. We anesthetized them and inserted a transesophageal echocardiographic (TEE) probe. Then we performed a transverse thoracotomy, attempting to produce acute mitral regurgitation (MR). In models that showed cardiac arrest we initiated OCCPR to restore cardiac function. The regurgitant area of mitral jet and left ventricular (LV) diameters and volumes were calculated before and during OCCPR using TEE. RESULTS: Ventricular fibrillation and/or electromechanical dissociation occurred in 13 animals (45%). In 4 models without preexisting MR, no additional regurgitation was detected during OCCPR, while in another 5 with preexisting MR we noticed a slight increase in the regurgitant flow. The regurgitant flow area changed from 0.62 +/- 1 cm2 before to 1.1 +/- 0.36 cm2 during OCCPR (p<0.008). In the 4 animals that had severe damage to the mitral apparatus after the attempts, the regurgitant flow increased from 4.01 +/- 0.93 cm2 to 7.7 +/- 2.6 cm2 (p<0.002). The LV transverse diameter decreased from 4.39 +/- 0.62 cm to 1.54 +/- 0.5 cm and its volume from 60.5 +/- 7.14 cm3 to 17.02 +/- 4.14 cm3 (both p<0.001), thus showing the effectiveness of OCCPR. CONCLUSIONS: Given the presence of preexisting mitral regurgitation, direct cardiac massage during OCCPR would probably be less effective than expected, because of an increase in the amount of the regurgitant.

The impact of aspirin resistance on the long-term cardiovascular mortality in patients with non-ST segment elevation acute coronary syndromes.

BACKGROUND: Aspirin resistance has been associated with an adverse long-term outcome in patients with atherosclerotic coronary artery disease, but more studies are needed. HYPOTHESIS: The aim of this study was to investigate the impact of aspirin resistance, assessed by the Platelet Function Analyzer-100 (PFA-100) (Dade Behring Inc., Deerfield, Ill., USA) on the long-term prognosis in patients with non-ST segment elevation acute coronary syndromes (NSTE-ACS). METHODS: A total of 496 consecutive patients were studied. The 1-y incidence of cardiovascular death was the prespecified study endpoint. The patients were divided, according to the values of PFA-100 collagen epinephrine closure time (CEPI-CT) upon presentation, into aspirin sensitives (those with a PFA-100 CEPI-CT>193 sec) and aspirin resistants (those with a PFA-100 CEPI-CT

Comparative performance of three metabolic syndrome definitions in the prediction of acute coronary syndrome.

OBJECTIVE: The value of the recently introduced definitions of metabolic syndrome (MetS) in the identification of high cardiovascular risk subjects remains questionable. We examined the association among different definitions of MetS, and the occurrence of a first-ever acute coronary syndrome (ACS). METHODS: We studied 211 patients with a first-ever ACS and 210 control subjects. We recorded cardiovascular risk factors and the presence of MetS using 3 different definitions, according to the National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III, National Heart, Lung and Blood Institute/American Heart Association (NHLBI/AHA), and International Diabetes Federation (IDF), respectively. The association of MetS with ACS was assessed using univariate and multivariate logistic regression models after adjusting for potential confounding factors, such as gender, age, body mass index, hypertension, diabetes mellitus, and lipids. RESULTS: ACS cases had a prevalence of metabolic syndrome according to NCEP-ATP III, NHLBI/AHA, and IDF criteria of 72.5%, 81.2%, and 79.1%, respectively. The unadjusted odds ratio (OR) for a first-ever ACS were 2.32 (95% CI: 1.53-3.52, p=0.001), 2.82 (95% CI: 1.79-4.43, p=0.001), and 3.26 (95% CI: 2.12-5.00, p=0.001) for NCEP-ATP III, NHLBI/AHA, and IDF MetS definitions, respectively. Multivariate analyses revealed that only IDF-defined MetS was significantly associated with ACS (OR: 2.23 95% CI: 1.30-3.82, p=0.003), while of the MetS components only waist circumference remained independently associated with ACS (O.R: 1.045 95% CI: 1.014-1.078, p=0.005). CONCLUSION: The definition of MetS according to the IDF criteria appears to be a better predictor of ACS than NCEP-ATP III and NHLBI/AHA.

Acute anterior myocardial infarction after multiple bee stings. A case of Kounis syndrome.

A 58-year-old man with no history of cardiac diseases or cardiovascular risk factors was stung by honeybees. Soon after, he gradually developed signs of an allergic reaction followed by severe retrosternal pain. Electrocardiographic, echocardiographic evidence and positive biochemical markers were consistent with an acute anterolateral myocardial infarction. Coronary arteriography showed a left anterior descending artery thrombotic lesion. This is a case of Kounis syndrome, which is the concurrence of acute coronary syndromes with conditions associated with mast cell activation including allergic or hypersensitivity reactions as well as anaphylactic or anaphylactoid insults. The clinical implications and pathophysiology of this dangerous association are discussed.

Diabetic myocardial disease: pathophysiology, early diagnosis and therapeutic options.

Diabetes mellitus is a powerful risk factor for cardiovascular disease associated with high morbidity and mortality rates. Diabetic patients also have an increased incidence of heart failure which has been traditionally attributed to the concurrent presence of ischemic or hypertensive heart disease. Yet, nowadays, according to recent scientific evidence, diabetic myocardial disease (DMD) is more and more being considered as a distinct nosologic entity, independent of the co-existence of coronary artery disease, arterial hypertension or other risk factors, with the potential to lead to a self-existent progressive development of heart failure. In this article, we review the possible pathophysiologic mechanisms involved in the development of DMD as well as the structural and functional changes in the diabetic heart. We emphasize the importance of early detection of the syndrome, especially by novel echocardiographic techniques. Finally, we refer to the various therapeutic options for the optimal management of DMD according to the recent literature.

Association of the 894G>T polymorphism in the endothelial nitric oxide synthase gene with risk of acute myocardial infarction.

BACKGROUND: This study was designed to investigate the association of the 894G>T polymorphism in the eNOS gene with risk of acute myocardial infarction (AMI), extent of coronary artery disease (CAD) on coronary angiography, and in-hospital mortality after AMI. METHODS: We studied 1602 consecutive patients who were enrolled in the GEMIG study. The control group was comprised by 727 individuals, who were randomly selected from the general adult population. RESULTS: The prevalence of the Asp298 variant of eNOS was not found to be significantly and independently associated with risk of AMI (RR = 1.08, 95%CI = 0.77-1.51, P = 0.663), extent of CAD on angiography (OR = 1.18, 95%CI = 0.63-2.23, P = 0.605) and in-hospital mortality (RR = 1.08, 95%CI = 0.29-4.04, P = 0.908). CONCLUSION: In contrast to previous reports, homozygosity for the Asp298 variant of the 894G>T polymorphism in the eNOS gene was not found to be associated with risk of AMI, extent of CAD and in-hospital mortality after AMI.

The impact of circulating total homocysteine levels on long-term cardiovascular mortality in patients with acute coronary syndromes.

BACKGROUND: To evaluate the possible independent impact of circulating total homocysteine (tHcy) levels on long-term cardiovascular mortality, in patients with either ST-segment elevation myocardial infarction (STEMI), or non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS: A total of 458 STEMI and 476 NSTE-ACS patients who presented consecutively, within the first 12 and 24 h of index pain respectively were studied. Each cohort was divided according to tertiles of circulating tHcy levels upon presentation. Early (30 days) and late (31 days through 5 years) cardiovascular mortality was the predefined study endpoint. RESULTS: There was no difference in the risk of 30-day cardiovascular death among the tertiles of tHcy in patients with STEMI (7.2%, 8.5% and 12.4% for the first, second and third tertiles respectively; p(trend)=0.3) or NSTE-ACS (3.1%, 3.8% and 5.7% for the first, second and third tertiles respectively; p(trend)=0.5). Patients in the upper tHcy tertile were at significantly higher unadjusted risk of late (from 31 days trough 5 years) cardiovascular death than those in the other two tertiles in STEMI (23.4%, 27.9% and 41.8% for the first, second and third tertiles respectively; p(trend) <0.001), and NSTE-ACS (24.7%, 28.1% and 45.6% for the first, second and third tertiles respectively; p(trend) <0.001) cohorts. However, after adjustment for baseline differences, there was no significant difference in the risk of late cardiovascular death among tHcy tertiles in either cohort. When circulating tHcy levels were treated as a continuous variable, they were significantly associated with late cardiovascular death (p<0.001 for both cohorts) by univariate Cox regression analysis, but not by multivariate Cox regression analysis (p=0.8, and p=1 for STEMI and NSTE-ACS cohorts, respectively). CONCLUSIONS: Based on the present data circulating tHcy levels determined upon admission do not serve as an independent predictor of long-term cardiovascular mortality in patients with either STEMI or NSTE-ACS.

The impact of oral antiplatelet responsiveness on the long-term prognosis after coronary stenting.

BACKGROUND: Decreased responsiveness to oral antiplatelet drug therapy has been associated with an adverse outcome after coronary stenting (CS), but more studies are needed. The purpose of the present study was to prospectively evaluate this issue. METHODS: A total of 612 consecutive patients with stable or unstable coronary artery disease who underwent CS after at least 12 hours of aspirin and clopidogrel loading were studied. The study population was divided into responders and nonresponders to oral antiplatelet therapy, according to the values of preprocedural Platelet Function Analyzer-100 (Dade Behring, Marburg, Germany) collagen epinephrine closure time (CEPI-CT). In particular, responders were considered as patients with a CEPI-CT > 193 seconds and nonresponders as those with a CEPI-CT < or = 193 seconds. The 1-year incidence of the composite of cardiac death and rehospitalization for nonfatal myocardial infarction was the prespecified primary study end point. RESULTS: At 1 year, 9.1% of patients reached the primary end point. Nonresponders to oral antiplatelet therapy were at significantly higher risk for the primary end point (18.7% vs 7.6%) than responders. Nonresponsiveness to oral antiplatelet therapy was a predictor of the primary end point by both univariate (hazard ratio 2.7, 95% CI 1.6-4.5, P < .001) and multivariate (hazard ratio 2.5, 95% CI 1.6-3.8, P < .001) Cox regression analysis. CONCLUSION: Based on the present data, preprocedural responsiveness to oral antiplatelet therapy, assessed by Platelet Function Analyzer-100 CEPI-CT, is an independent predictor of long-term outcome after CS.

The impact of hs C-reactive protein and other inflammatory biomarkers on long-term cardiovascular mortality in patients with acute coronary syndromes.

We evaluated whether high circulating levels of serum amyloid A (SAA), fibrinogen, interleukin-6 (IL-6) or leukocytes count (LC), can provide any additional predictive value over that provided by hs C-reactive protein (hs-CRP) for the incidence of 5-year cardiovascular mortality, in 458 and 476 consecutive patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndromes (NSTE-ACS), respectively. By 5 years the incidence of cardiovascular mortality was 37.3% and 35.5% in patients with STEMI and NSTE-ACS, respectively. Each of the study inflammatory biomarkers conferred independent to clinical risk predictors (and to cardiac troponin I) long-term prognostic information (all p<0.05), but only LC provided additional predictive value over that provided by hs-CRP, in either cohort (p<0.05). By multivariate Cox regression analysis, hs-CRP (p<0.001 for both cohorts) and LC (p=0.009 and p<0.001 for STEMI and NSTE-ACS, respectively) were the only inflammatory biomarkers independently associated with the incidence of 5-year cardiovascular mortality. According to the present results high circulating levels of LC but not of SAA, fibrinogen or IL-6 can provide additional long-term predictive value over that provided by hs-CRP in patients with acute coronary syndromes.

Continuous 12-lead electrocardiographic ST monitoring and long-term prognosis after successful coronary stenting.

BACKGROUND: The possible long-term prognostic value of transient ST ischemic episodes detected by continuous multilead electrocardiographic (ECG) monitoring after successful coronary stenting (CS) has not been thoroughly investigated. METHODS: A total of 739 consecutive patients, who underwent a 24-hour, continuous 12-lead electrocardiographic (ECG) ST monitoring in the first day after successful CS, were studied. An ST ischemic episode was defined as a transient ST shift (depression or elevation) in any lead of > or = 0.10 mV compared with the reference ECG lasting for > or = 1 minute. RESULTS: The incidence of the composite of death, nonfatal myocardial infarction, and recurrent angina by the first year was 28.7%. Patients with > or = 3 (defined by receiver operating characteristics analysis) ST ischemic episodes, detected by continuous 12-lead ECG ST monitoring, were at significantly higher risk for the 1-year composite primary end point than those with either 1 and 2 (52.7% vs 25.7%, hazard ratio [HR] 2.1, 95% CI 1.4-3.7, P < .001) or no (52.7% vs 25%, HR 2.2, 95% CI 1.2-2.9, P < .001) ST ischemic episodes. By multivariate Cox regression analysis, the occurrence of > or = 3 ST ischemic episodes in the first postprocedural day was independently associated with a significant increased risk of the 1-year composite primary end point (HR 1.9, 95% CI 1.4-3.9, P = .002). CONCLUSIONS: The present study suggests that continuous 12-lead ECG ST monitoring in the first day after successful CS may serve as an affordable tool for the identification of patients with an increased risk of fatal or nonfatal ischemic complication during the first year after the procedure.