Timo Lenderink

Benefit of Thrombolytic Therapy is Sustained Throughout Five Years and Is Related to TIMI Perfusion Grade 3 But Not Grade 2 Flow at Discharge

BACKGROUND Long-term follow-up in patients treated with thrombolysis for acute myocardial infarction thus far has been reported in a few studies only, and no long-term follow-up is available for patients who underwent additional percutaneous transluminal coronary angioplasty (PTCA). This report describes 5-year survival as collected in patients who received placebo, recombinant tissue plasminogen activator (rTPA), or rTPA with additional immediate PTCA in two European Cooperative Study Group trials. Determinants for long-term survival were assessed in 1043 patients discharged alive. METHODS AND RESULTS Five-year follow-up information on mortality was collected. Hospital mortality was lower after rTPA than placebo (2.5% versus 5.7%, P = .04) and higher after rTPA with immediate PTCA compared with rTPA without additional intervention (6.0% versus 2.2%, P = .07). Of the 1043 hospital survivors, data were available for 923 patients, of whom 109 died. In the placebo group, mortality after hospital discharge was 10.7% versus 11.0% in the comparative rTPA group. The patients treated with rTPA and immediate PTCA had a mortality rate of 10.5% versus 8.9% in the rTPA group without PTCA (all P = NS). Significant determinants of mortality in multivariate proportional hazards analysis were enzymatic infarct size, indicators of residual left ventricular function, number of diseased vessels and TIMI perfusion grade at discharge. Patients with TIMI grade 2 flow had mortality rates similar to those with TIMI flow grades 0 and 1, while prognosis was better in patients with TIMI flow grade 3. CONCLUSIONS The initial in-hospital benefit of thrombolysis with intravenous rTPA is maintained throughout 5 years, with no early or late beneficial effect of systematic immediate PTCA. Enzymatic infarct size, left ventricular function, and extent of coronary artery disease are predictors for long-term survival. TIMI perfusion grade 2 at discharge should be considered as an inadequate result of therapy.

Reduction of Recurrent Ischemia With Abciximab During Continuous ECG-Ischemia Monitoring in Patients With Unstable Angina Refractory to Standard Treatment (CAPTURE)

BACKGROUND In the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina) trial, 1265 patients with refractory unstable angina were treated with abciximab or placebo, in addition to standard treatment from 16 to 24 hours preceding coronary intervention through 1 hour after intervention. To investigate the incidence of recurrent ischemia and the ischemic burden, a subset of 332 patients (26%) underwent continuous vector-derived 12-lead ECG-ischemia monitoring. METHODS AND RESULTS Patients were monitored from start of treatment through 6 hours after coronary intervention. Ischemic episodes were detected in 31 (18%) of the 169 abciximab and in 37 (23%) of the 163 placebo patients (NS). Only 9 (5%) of abciximab versus 22 (14%) of placebo patients had >/=2 ST episodes (P<0.01). In patients with ischemia, abciximab significantly reduced total ischemic burden (P<0.02), which was calculated alternatively as the total duration of ST episodes per patient, the area under the curve of the ST vector magnitude during episodes, or the sum of the areas under the curves of 12 leads during episodes. Twenty-one patients (6%) suffered a myocardial infarction (MI) (18) or died (3) within 5 days of treatment. The presence of asymptomatic and symptomatic ST episodes during the monitoring period preceding coronary intervention was associated with an increased relative risk of these events of 3.2 (95% CI 1.4, 7.4) and 4.1 (95% CI 1.4, 12.2), respectively. CONCLUSIONS Recurrent ischemia predicts MI or death within 5 days of follow-up. Treatment with abciximab is associated with a reduction of frequent ischemia and a reduction of total ischemic burden in patients with refractory unstable angina. As such, patients with ischemia derive particularly high benefit from abciximab.

Elevated troponin T and C-reactive protein predict impaired outcome for 4 years in patients with refractory unstable angina, and troponin T predicts benefit of treatment with abciximab in combination with PTCA

AIMS Treatment with the glycoprotein IIb/IIIa receptor antagonist abciximab before and during coronary intervention in refractory unstable angina improves early outcome. We collected 4-year follow-up data to assess whether this benefit is sustained. Additionally, we investigated the predictive value of baseline troponin T and CRP for long-term cardiovascular events. METHODS AND RESULTS Of 1265 patients enrolled in the CAPTURE trial follow-up was available in 94% of the patients alive after 6 months (median 48 months). Survival was similar in both groups. Both elevated troponin T and CRP were associated with impaired outcome, independently of other established risk factors, but with a different time course. Elevated troponin was associated with increased procedure related risk, and elevated CRP with increased risk for subsequent events. Lower rates of the composite end-point of death or myocardial infarction with abciximab vs. placebo were sustained during long-term follow up: 15.7% vs 17.2% at 4 years (P=ns), particularly in patients with elevated troponin T: 16.9% with abciximab vs 28.4% with placebo: P=0.015. Elevated CRP was not associated with specific benefit of abciximab. CONCLUSION Troponin T as a marker of thrombosis and CRP as a marker of inflammation are independent predictors of impaired outcome at 4 years follow-up. The initial benefit from abciximab with regard to death and myocardial infarction was preserved at 4 years. No specific benefit with abciximab was observed for patients with elevated CRP, suggesting that a chronic inflammatory process is not affected by abciximab. In contrast the benefit of treatment in patients with elevated troponin T implies that the acute thrombotic process in refractory unstable angina is treated effectively.

Multimarker risk model containing troponin-T, interleukin 10, myeloperoxidase and placental growth factor predicts long-term cardiovascular risk after non-ST-segment elevation acute coronary syndrome

Objective To evaluate the predictive value of seven biomarkers, which individually have been shown to be independent predictors, for use in a combined multimarker model for long-term cardiovascular outcome after non-ST-segment elevation acute coronary syndrome (NSTEACS). Design and Setting Levels of high-sensitivity C-reactive protein (hsCRP), myeloperoxidase, pregnancy-associated plasma protein A, placental growth factor (PlGF), soluble CD40 ligand (sCD40L), interleukin 10 (IL-10) and troponin-T (TnT) were determined in patients enrolled in the CAPTURE trial. Cox proportional hazard regression analyses were applied to evaluate the relation between biomarkers and the occurrence of all-cause mortality or non-fatal myocardial infarction (MI). Patients 1090 patients with NSTEACS. Main outcome measure All-cause mortality and non-fatal MI during a median follow-up of 4 years. Results The composite endpoint was reached by 15.3% of patients. Admission levels of TnT >0.01 μg/l (adjusted HR 1.8), IL-10 <3.5 ng/l (1.7), myeloperoxidase >350 μg/l (1.5) and PlGF >27 ng/l (1.9) remained significant predictors for the incidence of all-cause mortality or non-fatal MI after multivariable adjustment for other biomarkers and clinical characteristics, whereas hsCRP, pregnancy-associated plasma protein A and sCD40L were only associated with the endpoint in univariate analysis. A multimarker model consisting of TnT, IL-10, myeloperoxidase and PlGF predicted 4-year event rates that varied between 6.0% (all markers normal) and 35.8% (three or more biomarkers abnormal). Conclusion In patients with NSTEACS, biomarkers characterising distinct aspects of the underlying atherosclerotic process and myocardial damage of the initial cardiac event can assist in predicting long-term adverse cardiac outcomes. The use of combinations of selected biomarkers adds incremental predictive value to further risk stratification in an otherwise seemingly homogeneous NSTEACS population.

Continuous ST-segment monitoring associated with infarct size and left ventricular function in the GUSTO-I trial.

BACKGROUND The aim of this study was to evaluate whether in patients with myocardial infarction, the intensity and duration of myocardial ischemia as measured by continuous ST monitoring are associated with infarct size and residual left ventricular function. METHODS AND RESULTS The analyses included patients with myocardial infarction, receiving thrombolytic therapy, who were enrolled in the electrocardiographic substudy of GUSTO-I, monitored by a vector-derived 12-lead electrocardiographic recording system, and in whom either infarct size (defined as cumulative release of alpha-hydroxybutyrate dehydrogenase activity per liter of plasma over a 72-hour period [Q(72)]) or left ventricular ejection fraction (LVEF) was determined. With the use of linear regression analysis, we investigated the association of various ST-trend characteristics with Q(72) (206 patients) and with LVEF (180 patients). A higher area under the ST trend since thrombolysis until 50% ST recovery and a higher area under recurrent ischemic episodes (ST reelevations) were significantly associated with a higher Q(72), whereas only a higher area under recurrent ischemic episodes was significantly associated with a lower LVEF. These associations remained after adjusting for other patient characteristics such as age, sex, infarct location, and time to treatment. CONCLUSIONS These findings support the physiologic hypothesis that both the intensity and duration of myocardial ischemia (both reflected by the estimated areas under the ST-trend curve) determine myocardial damage and thus are associated with infarct size and ejection fraction in patients with acute myocardial infarction who receive thrombolytic therapy.

Prediction of 30-day mortality in older patients with a first acute myocardial infarction.

Objectives: This study sought predictors of mortality in patients aged ≥75 years with a first ST-segment elevation myocardial infarction (STEMI) and evaluated the validity of the GUSTO-I and TIMI risk models. Methods: Clinical variables, treatment and mortality data from 433 consecutive patients were collected. Univariable and multivariable logistic regression analyses were applied to identify baseline factors associated with 30-day mortality. Subsequently a model predicting 30-day mortality was created and compared with the performance of the GUSTO-I and TIMI models. Results: After adjustment, a higher Killip class was the most important predictor (OR 16.1; 95% CI 5.7–45.6). Elevated heart rate, longer time delay to admission, hyperglycemia and older age were also associated with increased risk. Patients with hypercholesterolemia had a significantly lower risk (OR 0.46; 95% CI 0.24–0.86). Discrimination (c-statistic 0.79, 95% CI 0.75–0.84) and calibration (Hosmer-Lemeshow 6, p = 0.5) of our model were good. The GUSTO-I and TIMI risk scores produced adequate discrimination within our dataset (c-statistic 0.76, 95% CI 0.71–0.81, and c-statistic 0.77, 95% CI 0.72–0.82, respectively), but calibration was not satisfactory (HL 21.8, p = 0.005 for GUSTO-I, and HL 20.6, p = 0.008 for TIMI). Conclusions: Short-term mortality in elderly patients with a first STEMI depends most importantly on initial clinical and hemodynamic status. The GUSTO-I and TIMI models are insufficiently adequate for providing an exact estimate of 30-day mortality risk.

Angiographic and clinical one-year follow-up of the Cordis tantalum coil stent in a multicenter international study demonstrating improved restenosis rates when compared to pooled PTCA and BENESTENT-I data: the European Antiplatelet Stent Investigation (EASI).

The Cordis tantalum coil stent was assessed in a nonrandomized multicenter trial: 275 patients with stable or unstable angina were entered. Clinical follow‐up was for 1 year, with repeat angiography at 6 months. The major adverse cardiac event rates (MACE) were 3%, 14%, and 17% at 1, 7, and 13 months, respectively. The procedural success rate was 96% and the subacute occlusion rate 1.5%, in a group of patients over 60% of whom had ACC/AHA type B2 or C lesions. The binary restenosis rate at 6 months was 17.3%. Minimum lumen diameter increased from 1.07 ± 0.28 mm preprocedure to 2.93 ± 0.34 mm poststenting and at 6 months was 1.99 ± 0.69 mm. These results demonstrate that the Cordis tantalum stent can be used to treat complex lesions with good procedural success and low rates of subacute thrombosis and restenosis at 6 months. Cathet Cardiovasc Intervent 2001;52:249–259.

Acute cardioversion vs a wait-and-see approach for recent-onset symptomatic atrial fibrillation in the emergency department: Rationale and design of the randomized ACWAS trial

Background Current standard of care for patients with recent‐onset atrial fibrillation (AF) in the emergency department aims at urgent restoration of sinus rhythm, although paroxysmal AF is a condition that resolves spontaneously within 24 hours in more than 70% of the cases. A wait‐and‐see approach with rate‐control medication only and when needed cardioversion within 48 hours of onset of symptoms is hypothesized to be noninferior, safe, and cost‐effective as compared with current standard of care and to lead to a higher quality of life. Design The ACWAS trial (NCT02248753) is an investigator‐initiated, randomized, controlled, 2‐arm noninferiority trial that compares a wait‐and‐see approach to the standard of care. Consenting adults with recent‐onset symptomatic AF in the emergency department without urgent need for cardioversion are eligible for participation. A total of 437 patients will be randomized to either standard care (pharmacologic or electrical cardioversion) or the wait‐and‐see approach, consisting of symptom reduction through rate control medication until spontaneous conversion is achieved, with the possibility of cardioversion within 48 hours after onset of symptoms. Primary end point is the presence of sinus rhythm on 12‐lead electrocardiogram at 4 weeks; main secondary outcomes are adverse events, total medical and societal costs, quality of life, and cost‐effectiveness for 1 year. Conclusions The ACWAS trial aims at providing evidence for the use of a wait‐and‐see approach for patients with recent‐onset symptomatic AF in the emergency department.

Cohort profile of BIOMArCS: the BIOMarker study to identify the Acute risk of a Coronary Syndrome-a prospective multicentre biomarker study conducted in the Netherlands

Purpose Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such ‘vulnerable periods’. Participants BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor. Methods and analysis We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate ‘vulnerable periods’ during which patients with CAD are at high short-term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for non-fatal ACS had occurred in 50 patients. A case–cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS. Future plans and dissemination Follow-up and event adjudication have been completed. Prespecified biomarker analyses are currently being performed and dissemination through peer-reviewed publications and conference presentations is expected from the third quarter of 2016. Should identification of a ‘vulnerable period’ prove to be feasible, then future research could focus on event reduction through pharmacological or mechanical intervention during such periods of high risk for ACS. Trial registration number NTR1698 and NTR1106.

Acute Anterior Wall Myocardial Infarction during Pregnancy in a 36-Year Old Patient

Acute myocardial infarction during pregnancy is a rare clinical condition. We present a case of a 36-year old woman in her 36th week of pregnancy with an acute anterior ST-elevated myocardial infarction (STEMI) caused by an occlusive proximal LAD. First treatment was thrombosuction, followed by placement of a bioresolvable vascular scaffold. Because of post procedural fetal bradycardia an emergency cesarean section was performed on the same day, despite all antithrombotic medications.