Patrick M.J. Verhorst

Third-generation zotarolimus-eluting and everolimus-eluting stents in all-comer patients requiring a percutaneous coronary intervention (DUTCH PEERS): a randomised, single-blind, multicentre, non-inferiority trial

BACKGROUND Third-generation, permanent-polymer-based drug-eluting stents with novel, flexible designs might be more easily delivered than previous generations of stents in complex coronary lesions, but might be less longitudinally stable. We aimed to assess the safety and efficacy in all-comer patients of two third-generation stents that are often used clinically, but that have not yet been compared, and one of which has not previously been assessed in a randomised trial. METHODS In this investigator-initiated, single-blind, multicentre, randomised, two-arm, non-inferiority trial, patients aged 18 years and older who required a percutaneous coronary intervention with implantation of a drug-eluting stent were recruited from four study sites in the Netherlands. We randomly assigned patients by independently managed computer-generated allocation sequences in a 1:1 ratio to receive either cobalt-chromium-based zotarolimus-eluting stents (Resolute Integrity, Medtronic, Santa Rosa, CA, USA) or platinum-chromium-based everolimus-eluting stents (Promus Element, Boston Scientific, Natick, MA, USA). Patients and analysts were masked to the allocated stent, but treating clinicians were not. The primary endpoint of target-vessel failure was a composite of safety (cardiac death or target-vessel-related myocardial infarction) and efficacy (target-vessel revascularisation) at 12 months, analysed by intention to treat (with a non-inferiority margin of 3·6%). This trial is registered with ClinicalTrials.gov, number NCT01331707. FINDINGS Between Nov 25, 2010, and May 24, 2012, 1811 eligible all-comer patients, with 2371 target lesions, were enrolled in the study. 370 (20%) patients presented with ST-elevation myocardial infarction and 447 (25%) with non-ST-elevation myocardial infarction. 906 patients were assigned to receive zotarolimus-eluting stents and 905 to receive everolimus-eluting stents. Ease of stent delivery was shown by very low numbers of patients requiring treatment other than their assigned study treatment (six [1%] in the zotarolimus-eluting stent group vs five [1%] in the everolimus-eluting stent group; p=0·22). 12-month follow-up results were available for 1810 patients (one patient in the zotarolimus-eluting stent group withdrew consent). The primary endpoint was met by 55 (6%) of 905 patients in the zotarolimus-eluting stent group and 47 (5%) of 905 in the everolimus-eluting stent group. The zotarolimus-eluting stent was non-inferior to the everolimus-eluting stent (absolute risk difference 0·88%, 95% CI -1·24% to 3·01%; upper limit of one-sided 95% CI 2·69%; non-inferiority p=0·006). We noted no significant between-group differences in individual components of the primary endpoint. Definite stent thrombosis occurred in three (0·3%) patients in the zotarolimus-eluting stent group and six (0·7%) patients in the everolimus-eluting stent group (p=0·34). Longitudinal stent deformation was seen only in the everolimus-eluting stent group (nine [1·0%] of 905 vs 0 of 906, p=0·002; nine of 1591 [0·6%] everolimus-eluting stents implanted became deformed), but was not associated with any adverse events. INTERPRETATION Both stents were similarly efficacious and safe, and provided excellent clinical outcomes, especially in view of the large number of patients who presented with acute myocardial infarctions. FUNDING Boston Scientific, Medtronic.

Left atrial appendage flow velocity assessment using transesophageal echocardiography in nonrheumatic atrial fibrillation and systemic embolism

Fifty-four patients with nonrheumatic atrial fibrillation (AF) were studied: 16 patients with (group I) and 38 patients without (group II) documented systemic embolism. Transesophageal echocardiography (TEE) was performed to evaluate the presence of left atrial (LA) appendage thrombus and LA spontaneous contrast, LA size, systolic and diastolic peak velocity of the left pulmonary vein, and forward and backward peak velocity of the LA appendage. No difference was observed in the presence of LA thrombus between the 2 groups. The occurrence of LA spontaneous contrast was significantly (p = 0.01) higher in the group with embolism. LA size, measured by atrial length (4.96 +/- 0.84 vs 4.79 +/- 1.38 cm; p = NS) and atrial width (4.50 +/- 0.96 vs 4.31 +/- 1.24 cm; p = NS), was the same for both groups and thus not associated with embolism. There was no difference in systolic peak velocity (0.39 +/- 0.22 vs 0.44 +/- 0.22 m/s; p = NS), and a trend toward a higher diastolic peak velocity (0.50 +/- 0.17 vs 0.42 +/- 0.15 m/s; p = 0.08) was seen in the left pulmonary vein in the group with embolism. Forward (0.25 +/- 0.19 vs 0.39 +/- 0.23 m/s; p < 0.05) and backward (0.23 +/- 0.15 vs 0.33 +/- 0.16 m/s; p < 0.05) peak velocities of the LA appendage were significantly lower in the embolism group. Assessment of LA appendage flow velocity may potentially identify patients with nonrheumatic AF at high risk for systemic embolism.

Tissue plasminogen activator activity and inhibition in acute myocardial infarction and angiographically normal coronary arteries

Parameters of blood coagulation, blood platelet reactivity and fibrinolysis were analyzed in 18 patients with acute myocardial infarction (AMI) and angiographically normal coronary arteries. This study group was compared with a patient control group of 18 AMI patients with 1-vessel obstructive coronary artery disease. Patients were matched for sex, age and AMI date. A healthy control group consisted of 18 sex- and age-matched volunteers. Blood coagulation measurements and platelet reactivity were similar in the 3 groups, except for fibrinogen, which was significantly higher in the patient control group. Plasma activity of tissue plasminogen activator (tPA) was detectable in only 2 patients in the study group, 9 in the patient control group (p less than 0.02) and 12 in the healthy control group (p less than 0.0001). Median plasma tPA inhibitory activity was higher in the study group (10.3 IU/ml) and the patient control group (8.1 IU/ml) than in the healthy control group (2.7 IU/ml, p less than 0.0001 and p less than 0.03). Thus, reduced activity and enhanced inhibition of plasma tPA may be important factors in the origin of coronary thrombosis, especially in the absence of coronary artery disease.

Transesophageal echocardiographic predictors for maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation

The aim of this study was to assess the value of transesophageal echocardiography (TEE) in patients with atrial fibrillation in predicting restoration and maintenance of sinus rhythm after electrical cardioversion. TEE was performed in 62 patients with atrial fibrillation before their first elective cardioversion. Clinical variables evaluated were: age, gender, duration, and etiology of atrial fibrillation. TEE variables included: left atrial (LA) length, width, and size, LA annulus size, as well as presence of LA spontaneous contrast, thrombus and mitral regurgitation, LA appendage size and flow, and left ventricular function. Based on initial outcome of cardioversion, patients were grouped into patients who remained in atrial fibrillation and in whom sinus rhythm was restored. The latter group of patients was followed for 1 year, and grouped into patients who reverted to atrial fibrillation and in whom sinus rhythm was maintained. Successful cardioversion was achieved in 50 of 62 patients (81%). None of the clinical or TEE variables were related to initial outcome. At 1-year follow-up, 29 of 50 patients (58%) who underwent successful cardioversion continued to have sinus rhythm. The following variables were related to maintenance of sinus rhythm: duration of atrial fibrillation (6.7 +/- 7.3 vs 2.0 +/- 2.4 months; p < 0.005); LA length (6.2 +/- 0.7 vs. 5.5 +/- 1.0 cm; p < 0.008); width (5.1 +/- 0.5 vs. 4.5 +/- 0.7 cm; p < 0.002); size (26.4 +/- 5.0 vs 19.8 +/- 6.5 cm2; p < 0.0005); annulus size (4.0 +/- 0.2 vs 3.7 +/- 0.3 cm; p < 0.0005); presence of LA spontaneous contrast (13 [62%] vs 4 [14%]; p < 0.002), and LA appendage flow (19 +/- 8 vs 36 +/- 15 cm/s; p < 0.0005). In multivariate logistic regression analysis, LA annulus size, but especially LA appendage flow, were significantly associated with maintenance of sinus rhythm. Thus, in TEE-guided electrical cardioversion of atrial fibrillation, variables often used to assess thromboembolic risk may also be used to predict 1-year outcome of cardioversion.

Myocardial viability: impact on left ventricular dilatation after acute myocardial infarction

Objective: To evaluate whether the presence of viable myocardium, detected by low dose dobutamine echocardiography, limits the likelihood of left ventricular dilatation in patients with acute myocardial infarction. Patients: 107 patients were studied by low dose dobutamine echocardiography at (mean (SD)) 3 (1) days after acute myocardial infarction. Cross sectional echocardiography was repeated three months later. Patients were divided in two groups based on the presence (n = 47) or absence (n = 60) of myocardial viability. Results: Baseline characteristics were comparable between the two groups, except for infarct location. Left ventricular end diastolic volume index (EDVI) was stable in patients with viability, but end systolic volume index (ESVI) decreased significantly (p = 0.006). Patients without viability had a significant increase in both EDVI (p < 0.0001) and ESVI (p = 0.0007). Subgroup analysis in patients with small and large infarcts (peak creatine kinase ≤ 1000 v > 1000 IU/l) showed that ventricular dilatation occurred only in patients with large infarcts without viability. This resulted in larger ESVI values at three months in that group compared with patients with large infarcts plus viability (p < 0.05). Multivariate regression analysis identified myocardial viability as an independent predictor of left ventricular dilatation, along with wall motion score index on low dose dobutamine echocardiography and the number of pathological Q waves. Conclusions: The presence of viability early after acute myocardial infarction is associated with preservation of left ventricular size, whereas the absence of viability results in ventricular dilatation, particularly in large infarcts.

In-hospital and long-term prognostic value of viable myocardium detected by dobutamine echocardiography early after acute myocardial infarction and its relation to indicators of left ventricular systolic dysfunction

The prognostic value of myocardial viability early after acute myocardial infarction (AMI) is still controversial, depending on the patient under study and the outcome end point considered. Furthermore, the relative prognostic importance of viability compared with indicators of systolic left ventricular (LV) dysfunction is not known. One hundred thirty-eight patients were studied with low-dose dobutamine echocardiography 3 +/- 1 days after AMI. Patients were divided in 2 groups based on presence (n = 55) or absence (n = 83) of myocardial viability and followed up for in-hospital and late cardiac events. During hospitalization, myocardial viability was the only independent predictor for recurrent ischemic events (chi-square 5.0, p = 0.025). End-systolic volume index and ejection fraction were both independent predictors of the occurrence of heart failure, whereas gender and end-systolic volume index emerged as independent predictors of hard cardiac events (death and sustained ventricular tachycardia). After hospital discharge, patients were followed for 19 +/- 7 months. Again, myocardial viability emerged as the only independent predictor of unstable angina (chi-square 7.7, p = 0.005). Age, hypertension, and ejection fraction were the most important independent predictors of hospitalization for heart failure, whereas ejection fraction was the only independent predictor of hard cardiac events. Presence of myocardial viability early after AMI is the single best predictor of recurrent in-hospital ischemic events and unstable angina after discharge. With respect to hard cardiac events and occurrence of heart failure, indicators of LV systolic dysfunction have a higher prognostic value than presence of myocardial viability.

Reduction of exercise-induced myocardial ischemia during add-on treatment with the angiotensin-converting enzyme inhibitor enalapril in patients with normal left ventricular function and optimal beta blockade☆

OBJECTIVES We sought to study the effect of angiotensin-converting enzyme inhibition on exercise-induced myocardial ischemia. BACKGROUND Although angiotensin-converting enzyme inhibitors have been shown to reduce ischemic events after myocardial infarction, few data are available regarding their direct anti-ischemic effects in patients with coronary artery disease. METHODS We studied 43 patients (average age 63 +/- 8 years) with exercise-induced myocardial ischemia (> or =0.1 mV ST depression, despite optimal beta blockade) and normal left ventricular function (ejection fraction >0.50). In a double-blind, placebo-controlled parallel design, patients were treated with angiotensin-converting enzyme inhibitor (enalapril 10 mg twice daily) or placebo. Assessments were made after three weeks (short-term) and 12 weeks (long-term). RESULTS At baseline, the groups were well matched for all clinical characteristics. After three weeks, there was a slight but not significant increase in time to 0.1 mV ST depression in both groups (p = NS); rate pressure product (RPP = heart rate x systolic blood pressure) was also unaffected. After 12 weeks, however, time to 0.1 mV ST depression further increased in the enalapril group (5.6 +/- 1.9 min) but was unchanged in the placebo group (4.4 +/- 1.3 min; p < 0.05 between groups). In contrast, RPP was not affected. Concentrations of both atrial and brain natriuretic peptides at peak exercise tended to be lower by enalapril, if compared to placebo (p = NS). CONCLUSIONS Angiotensin-converting enzyme inhibition may reduce exercise-induced myocardial ischemia in patients with normal left ventricular function. Further studies are needed to elucidate the mechanisms involved.

Early prediction of improvement in ejection fraction after acute myocardial infarction using low dose dobutamine echocardiography

Objective: To evaluate the relation between changes in ejection fraction during the first three months after acute myocardial infarction and myocardial viability. Patients: Myocardial viability was assessed using low dose dobutamine echocardiography in 107 patients at mean (SD) 3 (1) days after acute myocardial infarction. Cross sectional echocardiography was repeated three months later. Left ventricular volumes and ejection fraction were determined from apical views using the Simpson biplane formula. Results: In patients with viability, ejection fraction increased by 4.4 (4.3)%; in patients without viability it remained unchanged (0.04 (3.6)%; p < 0.001). A ≥ 5% increase in ejection fraction was present in 21 of 107 patients (20%). Receiver operating characteristic analysis showed that myocardial viability in ≥ 2 segments predicted this increase in ejection fraction with a sensitivity of 81% and a specificity of 65%. Multivariate logistic regression analysis was used to define which clinical and echocardiographic variables were related to ≥ 5% improvement in ejection fraction. Myocardial viability, non-Q wave infarction, and anterior infarction all emerged as independent predictors, myocardial viability being the best (χ2 = 14.5; p = 0.0001). Using the regression equation, the probability of ≥ 5% improvement in ejection fraction for patients with a non-Q wave anterior infarct with viability was 73%, and for patients with a Q wave inferior infarct without viability, only 2%. Conclusions: Myocardial viability after acute myocardial infarction is the single best predictor of improvement in ejection fraction. In combination with infarct location and Q wave presence, the probability of ≥ 5% improvement can be estimated in individual patients at the bedside.

TWENTE Study: The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twente: study design, rationale and objectives

Background. New-generation drug-eluting stents (DES) may solve several problems encountered with first-generation DES, but there is a lack of prospective head-to-head comparisons between new-generation DES. In addition, the outcome of regulatory trials may not perfectly reflect the outcome in ‘real world’ patients.Objectives. To compare the efficacy and safety of two new-generation DES in a ‘real world’ patient population.Methods. A prospective, randomised, single-blinded clinical trial to evaluate clinical outcome after Endeavor Resolute vs. Xience V stent implantation. The primary endpoint is target vessel failure at one-year follow-up. In addition, the study comprises a two-year and an open-label five-year follow-up. (Neth Heart J 2010;18:360-4.)

Exercise-induced syncope as late consequence of radiotherapy

This report describes a 34-year-old female with an exercise-induced atrioventricular block resulting from transient ischemia caused by a radiation-induced ostial stenosis of the right coronary artery. Patient first underwent coronary artery surgery with a right internal mammary artery to the right coronary artery. After 18 months she was readmitted with exercise-induced syncope due to graft occlusion. This time a successful rotablator procedure was performed on the ostial stenosis.