Effects of Acute Triiodothyronine Treatment in Patients with Anterior Myocardial Infarction Undergoing Primary Angioplasty: Evidence from a Pilot Randomized Clinical Trial (ThyRepair Study).

Background: Thyroid hormone has a differential action on healthy and ischemic heart. Triiodothyronine (T3) administration improved postischemic cardiac function while it limited apoptosis in experimentally induced ischemia. Thus, the present study investigated the potential effects of acute liothyronine (LT3) treatment in patients with anterior myocardial infarction. Methods: This study is a pilot, randomized, double-blind, placebo-controlled trial (ThyRepair study). We randomized 52 patients and analyzed data from 37 patients (n = 16 placebo and n = 21 LT3), per prespecified per protocol analysis. We excluded three patients who had died of cardiovascular causes (one in placebo and two in LT3 arm), four with small infarct size below a pre-specified threshold (in the placebo arm), and the rest, who lacked follow-up data. LT3 treatment started after stenting as an intravenous (i.v.) bolus injection of 0.8 µg/kg of LT3 followed by a constant infusion of 0.113 µg/kg/h i.v. for 48 hours. All patients had cardiac magnetic resonance (CMR) at hospital discharge and 6 months follow-up. The primary end point was CMR left ventricular (LV) ejection fraction (LVEF) and secondary endpoints were LV volumes, infarct volume (IV), and safety. Results: The CMR LVEF% at 6 months was 53.6 ± 9.5 for the LT3-treated group and 48.6 ± 11 for placebo, p = 0.15. Acute LT3 treatment resulted in a significantly lower LV end-diastolic volume index (92.2 ± 16.8 mL/m2 vs. 107.5 ± 22.2, p = 0.022) and LV systolic volume index (47.5 ± 13.9 mL/m2 vs. 61.3 ± 21.7, p = 0.024) at hospital discharge, but not at 6 months. There was no statistically significant difference in CMR IV at hospital discharge between the groups (p = 0.24). CMR IV tended to be lower in the LT3-treated group at 6 months (18.7 ± 9.5 vs. 25.9 ± 11.7, in placebo, p = 0.05). Serious, life-threatening events related to LT3 treatment were not observed. A tendency for an increased incidence of atrial fibrillation (AF) was found in the LT3 group during the first 48 hours (19% for T3 group vs. 5% for placebo, p = 0.13). Conclusion: This pilot randomized, placebo-controlled trial study suggests potential favorable effects (acute cardiac dilatation and 6-month IV) as well as potential concerns regarding a higher risk of AF after LT3 administration early after myocardial infarction, which should be tested in a larger scale study.

The incidence of recurrent cardiovascular events among acute coronary syndrome patients treated with generic or original clopidogrel in relation to their sociodemographic and clinical characteristics. The Aegean study.

INTRODUCTION: The use of generic drugs is continuously growing; however, there are limited epidemiological data regarding the therapeutic equivalence of each original drug formulation with its generic counterparts. We evaluated the 12-month composite endpoint of recurrent acute myocardial infarction, ischaemic stroke, cardiac deaths, or hospitalisation due to a major bleeding in acute coronary syndrome (ACS) patients treated with original clopidogrel or a generic clopidogrel formulation, in relation to sociodemographic and clinical characteristics. MATERIAL AND METHODS: Consecutive Greek ACS patients (n = 1194) hospitalised in the Aegean islands and the Attica region were enrolled. Clopidogrel treatment was recorded either as original clopidogrel hydrogen sulphate (Plavix®/Iscover®) or as a generic clopidogrel besylate formulation (Clovelen®). The composite endpoint was recorded at 12-month follow-up. RESULTS: The 12-month composite endpoint was 3.9% (4.6% in the Aegean islands and 3.5% in the Attica area, p > 0.05). The respective incidence in men was 4.0% and in women 3.8% (p > 0.05). Overall, generic and original clopidogrel use was 87% and 13% of patients, respectively. No significant differences were observed between original and generic clopidogrel use and 12-month composite endpoint incidence. Subgroup analysis with gender, region of residence, and clinical and lifestyle factors as strata did not reveal any significant outcomes. Haemorrhage incidence did not exceed 1% in the total sample. CONCLUSIONS: The use of a generic clopidogrel besylate formulation was quite high in both urban and insular areas of Greece and had similar efficacy and safety profile with the original clopidogrel salt, supporting the routine use of this low-cost generic clopidogrel in the management of cardiovascular disease patients.

Multicenter Randomized Evaluation of High Versus Standard Heparin Dose on Incident Radial Arterial Occlusion After Transradial Coronary Angiography: The SPIRIT OF ARTEMIS Study.

OBJECTIVES: The aim of this study was to test the hypothesis that more intensive over standard anticoagulation administered during coronary angiography would significantly reduce rates of radial artery occlusion (RAO). BACKGROUND: RAO, although silent, remains a frequent and therefore worrisome complication following transradial coronary angiography. Anticoagulation is effective in reducing RAO, but the optimal heparin dose remains ill defined. METHODS: In this multicenter, randomized superiority trial, a high dose (100 IU/kg body weight administered in divided doses) and a standard dose (50 IU/kg body weight) of heparin during 5- or 6-F coronary angiography were compared. A total of 3,102 patients were randomized, of whom 1,836 patients not proceeding to percutaneous coronary intervention and without need for arterial access crossover entered the trial. Post-catheterization hemostasis did not follow a rigid protocol. RESULTS: A total of 102 early RAOs were found on ultrasonography (incidence 5.6%). In the high-dose heparin group, the rate of RAO was significantly lower compared with the standard-dose heparin group (27 [3.0%] vs. 75 [8.1%]; odds ratio: 0.35; 95% confidence interval: 0.22 to 0.55; p < 0.001), without compromising safety. The time to achieve hemostasis was similar between groups. To avoid 1 RAO, the number of patients needed to treat in the high-dose heparin group was approximately 20. These results were corroborated by our integrated database, showing an 80% reduction of forearm artery occlusions in high versus low heparin dose patients and our updated meta-analysis of randomized controlled trials demonstrating significant benefit of higher over lower anticoagulation intensity. CONCLUSIONS: High compared with standard heparin dose significantly reduced the rate of RAO in patients undergoing coronary angiography. High-intensity anticoagulation should be considered in transradial diagnostic procedures. (High [100IU/Kg] Versus Standard [50IU/Kg] Heparin Dose for Prevention of Forearm Artery Occlusion; NCT02570243).

New-onset atrial fibrillation and clinical outcome in non-cardiac intensive care unit patients.

BACKGROUND: Data regarding new onset atrial fibrillation (nAF) in general, non-cardiac, intensive care unit (ICU) patients are limited. However, it has been suggested that nAF is associated with worse clinical outcome in these patients. OBJECTIVE: The purpose of the present work was to study the prognostic impact of nAF, in this setting. METHODS: We prospectively studied all patients admitted to a single ICU for a period of 12 months. Patients admitted for brief post-operative monitoring, patients with chronic, intermittent atrial fibrillation and atrial fibrillation present upon admission, were excluded. Death during ICU stay (ICUD) was the pre-specified study end-point. Length of stay (LOS) for survivors was also reported. A number of factors related to the occurrence of nAF and the present disease were recorded for each patient. RESULTS: The study population was comprised of 133 patients. Twenty (15%) of them manifested nAF. The end-point of ICUD was observed in 27.1% of the patients. The median LOS reported was 8 days. Patients with nAF seemed to have significantly worse prognosis, compared to those who did not manifest nAF (OR=3.35, 95%CI:1.26-8.92; P=0.016). Additionally, nAF patients appear to require significantly extended LOS (P=0.01). Nevertheless, when the effect of nAF on ICUD was adjusted for sepsis, there was no statistically significant difference between those that manifested nAF and the rest of the patients. CONCLUSION: Patients suffering nAF seem to have worse prognosis during ICU stay. However, a direct impact of nAF on mortality was not documented.

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.

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 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

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.

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.

Association of inflammatory biomarkers and cardiac troponin I with multifocal activation of coronary artery tree in the setting of non-ST-elevation acute myocardial infarction.

We evaluated the possible association of the serum levels of C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, and cardiac troponin I (cTnI) with the presence of complex angiographic characteristics throughout the coronary artery tree in 519 consecutive patients with non-ST-elevation acute myocardial infarction (NSTEMI). Blood samples were obtained in the first 12h of NSTEMI invasion and all patients underwent in-hospital coronary angiography. Coronary lesions were classified as complex lesion (CL) or non-CL according to Ambrose criteria. Serum levels of CRP (p<0.001), SAA (p<0.001), or fibrinogen (p=0.001), but not of cTnI (p=0.9), were significantly related to the presence of multiple (> or =2) CLs. On the contrary, serum levels of cTnI (p<0.001), but not of CRP (p=0.5), SAA (p=0.9), or fibrinogen (p=0.9), were significantly associated with the severity of coronary artery disease. The results of the present study suggest that elevated levels of inflammatory biomarkers are associated with a generalized activation of coronary artery tree while elevated cTnI levels are associated with the severity of coronary artery disease in the setting of NSTEMI. It seems that inflammatory biomarkers and cTnI reflect different aspect of the process involved in unstable coronary artery disease.

Early prognostic usefulness of C-reactive protein added to the Thrombolysis In Myocardial Infarction risk score in acute coronary syndromes.

The aim of the present study was to evaluate whether an elevated plasma C-reactive protein (CRP) level provides any additional prognostic information to the validated Thrombolysis In Myocardial Infarction (TIMI) risk score in patients with acute coronary syndromes. For this purpose, 1,846 consecutive patients with either acute ST-segment elevation myocardial infarction (STEMI; 861 patients) or non-ST-segment elevation acute coronary syndrome (NSTEACS; 985 patients) were included. The incidence of 30-day death and 14-day composite of death, myocardial infarction (or repeat myocardial infarction) and recurrent ischemia was the prespecified primary end point in the STEMI and NSTEACS cohorts, respectively. The incidence of the primary end point was 9.8% and 23.6% in the STEMI and NSTEACS cohorts, respectively. A significantly increased risk of the primary end point was present with an increase in the STEMI and NSTEACS TIMI risk score (p(trend) < 0.001 for the 2 groups). A plasma CRP value of > or = 5 and > or = 3 mg/L (defined by receiver-operating characteristic analysis) was associated with a significantly increased risk of the primary end point in the STEMI and NSTEACS cohorts, respectively (p < 0.001 for the 2 cohorts), and it was true throughout the subgroups of STEMI and NSTEACS TIMI risk scores. In conclusion, an elevated plasma CRP level appears to be a marker that adds prognostic information to the validated STEMI and NSTEACS TIMI risk score. The plasma CRP and TIMI risk score may be used together for enhanced risk stratification in the setting of acute coronary syndromes.

Continuous 12-lead electrocardiographic ST monitoring adds prognostic information to the thrombolysis in myocardial infarction risk score in patients with non-ST-elevation acute coronary syndromes.

BACKGROUND: Continuous 12-lead electrocardiographic (ECG) ST monitoring and the Thrombolysis In Myocardial Infarction Risk Score (TIMI-RS), both have been shown to be useful for early risk stratification in patients with non-ST elevation acute coronary syndromes (NSTACS). HYPOTHESIS: Transient ST ischemic events, detected by continuous 12-lead ECG ST monitoring, early in the course of NSTACS, may add prognostic information to the TIMI-RS. METHODS: In all, 567 consecutive patients with a NSTACS underwent 24-h continuous 12-lead ECG ST monitoring. An ST ischemic event was defined as a transient ST shift in any lead of > or = 0.10 mV compared with the reference ECG, lasting for > or = 1 min. RESULTS: The incidence of the composite of death, nonfatal myocardial infarction (or reinfarction) and recurrent ischemia by Day 14 was 22.2%. By Day 30, the incidence of the composite of death and nonfatal myocardial infarction (or reinfarction) was 14.7%. There was a significantly increased risk of 14-day (p value for trend < 0.001) or 30-day (p value for trend <0.001) composite endpoint with increasing of TIMI-RS. Moreover, the occurrence of > or = 1 ST shifts during ST monitoring was associated with a significantly increased risk of 14- (p value < 0.001) or 30-day (p value < 0.001) composite endpoint, and this was true throughout the groups of TIMI-RS. CONCLUSIONS: The present study suggests that continuous 12-lead ECG ST monitoring, early in the course of NSTACS, may serve as an affordable tool to add prognostic information to the TIMI-RS.