Ad F.M. van den Heuvel

Thrombus aspiration during primary percutaneous coronary intervention.

BACKGROUND Primary percutaneous coronary intervention (PCI) is effective in opening the infarct-related artery in patients with myocardial infarction with ST-segment elevation. However, the embolization of atherothrombotic debris induces microvascular obstruction and diminishes myocardial reperfusion. METHODS We performed a randomized trial assessing whether manual aspiration was superior to conventional treatment during primary PCI. A total of 1071 patients were randomly assigned to the thrombus-aspiration group or the conventional-PCI group before undergoing coronary angiography. Aspiration was considered to be successful if there was histopathological evidence of atherothrombotic material. We assessed angiographic and electrocardiographic signs of myocardial reperfusion, as well as clinical outcome. The primary end point was a myocardial blush grade of 0 or 1 (defined as absent or minimal myocardial reperfusion, respectively). RESULTS A myocardial blush grade of 0 or 1 occurred in 17.1% of the patients in the thrombus-aspiration group and in 26.3% of those in the conventional-PCI group (P<0.001). Complete resolution of ST-segment elevation occurred in 56.6% and 44.2% of patients, respectively (P<0.001). The benefit did not show heterogeneity among the baseline levels of the prespecified covariates. At 30 days, the rate of death in patients with a myocardial blush grade of 0 or 1, 2, and 3 was 5.2%, 2.9%, and 1.0%, respectively (P=0.003), and the rate of adverse events was 14.1%, 8.8%, and 4.2%, respectively (P<0.001). Histopathological examination confirmed successful aspiration in 72.9% of patients. CONCLUSIONS Thrombus aspiration is applicable in a large majority of patients with myocardial infarction with ST-segment elevation, and it results in better reperfusion and clinical outcomes than conventional PCI, irrespective of clinical and angiographic characteristics at baseline. (Current Controlled Trials number, ISRCTN16716833.)

Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy.

OBJECTIVES We performed positron emission tomography (PET) to evaluate myocardial ischemia in patients with idiopathic dilated cardiomyopathy (IDC). BACKGROUND Patients with IDC have anatomically normal coronary arteries, and it has been assumed that myocardial ischemia does not occur. METHODS We studied 22 patients with IDC and 22 control subjects using PET with nitrogen-13 ammonia to measure myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia. To investigate glucose metabolism, fluorine-18 deoxyglucose (18FDG) was used. For imaging of oxygen consumption, carbon-11 acetate clearance rate constants (k(mono)) were assessed at rest and during submaximal dobutamine infusion (20 microg/kg body weight per min). RESULTS Global MBF reserve (dipyridamole-induced) was impaired in patients with IDC versus control subjects (1.7 +/- 0.21 vs. 2.7 +/- 0.10, p < 0.05). In patients with IDC, MBF reserve correlated with left ventricular (LV) systolic wall stress (r = -0.61, p = 0.01). Furthermore, in 16 of 22 patients with IDC (derived by dipyridamole perfusion) mismatch (decreased flow/increased 18FDG uptake) was observed in 17 +/- 8% of the myocardium. The extent of mismatch correlated with LV systolic wall stress (r = 0.64, p = 0.02). The MBF reserve was lower in the mismatch regions than in the normal regions (1.58 +/- 0.13 vs. 1.90 +/- 0.18, p < 0.05). During dobutamine infusion k(mono) was higher in the mismatch regions than in the normal regions (0.104 +/- 0.017 vs. 0.087 +/- 0.016 min(-1), p < 0.05). In the mismatch regions 18FDG uptake correlated negatively with rest k(mono) (r = -0.65, p < 0.05), suggesting a switch from aerobic to anaerobic metabolism. CONCLUSIONS Patients with IDC have a decreased MBF reserve. In addition, low MBF reserve was paralleled by high LV systolic wall stress. These global observations were associated with substantial myocardial mismatch areas showing the lowest MBF reserves. In geographically identical regions an abnormal oxygen consumption pattern was seen together with a switch from aerobic to anaerobic metabolism. These data support the notion that regional myocardial ischemia plays a role in IDC.

Intracoronary Versus Intravenous Administration of Abciximab in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention With Thrombus Aspiration: The Comparison of Intracoronary Versus Intravenous Abciximab Administration During Emergency Reperfusion of ST-Segment Elevation Myocardial Infarction (CICERO) Trial

Background— Administration of the glycoprotein IIb/IIIa inhibitor abciximab is an effective adjunctive treatment strategy during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Although small-scale studies have suggested beneficial effects of intracoronary over intravenous administration of abciximab, this has not been investigated in a medium-scale randomized clinical trial. Methods and Results— A total of 534 ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration within 12 hours of symptom onset were randomized to either an intracoronary or an intravenous bolus of abciximab (0.25 mg/kg). Patients were pretreated with aspirin, heparin, and clopidogrel. The primary end point was the incidence of restored myocardial reperfusion, defined as complete ST-segment resolution. Secondary end points included myocardial reperfusion as assessed by myocardial blush grade, enzymatic infarct size, and major adverse cardiac events at 30 days. The incidence of complete ST-segment resolution was similar in the intracoronary and intravenous groups (64% versus 62%; P=0.562). However, the incidence of myocardial blush grade 2/3 was higher in the intracoronary group than in the intravenous group (76% versus 67%; P=0.022). Furthermore, enzymatic infarct size was smaller in the intracoronary than in the intravenous group (P=0.008). The incidence of major adverse cardiac events was similar in both groups (5.5% versus 6.1%; P=0.786). Conclusions— In ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration, intracoronary administration of abciximab compared with intravenous administration does not improve myocardial reperfusion as assessed by ST-segment resolution. However, intracoronary administration is associated with improved myocardial reperfusion as assessed by myocardial blush grade and a smaller enzymatic infarct size. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00927615.

Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial

IMPORTANCE Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function. OBJECTIVE To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI). DESIGN, SETTING, AND PARTICIPANTS Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013. INTERVENTIONS Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months. MAIN OUTCOMES AND MEASURES The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure. RESULTS At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed. CONCLUSIONS AND RELEVANCE Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01217307.

Effect of High-Dose Intracoronary Adenosine Administration During Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction A Randomized Controlled Trial

BACKGROUND Coronary microvascular dysfunction is frequently seen in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention. Previous studies have suggested that the administration of intravenous adenosine resulted in an improvement of myocardial perfusion and a reduction in infarct size. Intracoronary adenosine (bolus of 30 to 60 microg) is a guideline-recommended therapy to improve myocardial reperfusion. The effect of intracoronary adenosine during primary percutaneous coronary intervention has not been investigated in a large randomized trial. METHODS AND RESULTS Patients presenting with acute ST-elevation myocardial infarction were randomized to 2 bolus injections of intracoronary adenosine (2 x 120 microg in 20 mL NaCl) or placebo (2 x 20 mL NaCl). The first bolus injection was given after thrombus aspiration and the second after stenting of the infarct-related artery. The primary end point was the incidence of residual ST-segment deviation <0.2 mV, 30 to 60 minutes after percutaneous coronary intervention. Secondary end points were ST-segment elevation resolution, myocardial blush grade, Thrombolysis in Myocardial Infarction flow on the angiogram after percutaneous coronary intervention, enzymatic infarct size, and clinical outcome at 30 days. A total of 448 patients were randomized to intracoronary adenosine (N=226) or placebo (N=222). The incidence of residual ST-segment deviation <0.2 mV did not differ between patients randomized to adenosine or placebo (46.2% versus 52.2%, P=NS). In addition, there were no significant differences in secondary outcome measures. CONCLUSIONS In this randomized placebo controlled trial enrolling 448 patients with ST-elevation myocardial infarction, administration of intracoronary adenosine after thrombus aspiration and after stenting of the infarct-related artery did not result in improved myocardial perfusion.

Effect of High-Dose Intracoronary Adenosine Administration During Primary Percutaneous Coronary Intervention in Acute Myocardial InfarctionCLINICAL PERSPECTIVE

BACKGROUND Coronary microvascular dysfunction is frequently seen in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention. Previous studies have suggested that the administration of intravenous adenosine resulted in an improvement of myocardial perfusion and a reduction in infarct size. Intracoronary adenosine (bolus of 30 to 60 microg) is a guideline-recommended therapy to improve myocardial reperfusion. The effect of intracoronary adenosine during primary percutaneous coronary intervention has not been investigated in a large randomized trial. METHODS AND RESULTS Patients presenting with acute ST-elevation myocardial infarction were randomized to 2 bolus injections of intracoronary adenosine (2 x 120 microg in 20 mL NaCl) or placebo (2 x 20 mL NaCl). The first bolus injection was given after thrombus aspiration and the second after stenting of the infarct-related artery. The primary end point was the incidence of residual ST-segment deviation <0.2 mV, 30 to 60 minutes after percutaneous coronary intervention. Secondary end points were ST-segment elevation resolution, myocardial blush grade, Thrombolysis in Myocardial Infarction flow on the angiogram after percutaneous coronary intervention, enzymatic infarct size, and clinical outcome at 30 days. A total of 448 patients were randomized to intracoronary adenosine (N=226) or placebo (N=222). The incidence of residual ST-segment deviation <0.2 mV did not differ between patients randomized to adenosine or placebo (46.2% versus 52.2%, P=NS). In addition, there were no significant differences in secondary outcome measures. CONCLUSIONS In this randomized placebo controlled trial enrolling 448 patients with ST-elevation myocardial infarction, administration of intracoronary adenosine after thrombus aspiration and after stenting of the infarct-related artery did not result in improved myocardial perfusion.

Percutaneous Edwards SAPIEN valve implantation in the tricuspid position: case report and review of literature

AIMS Experience with transcatheter valve-in-valve implantation in a failing bioprosthetic tricuspid valve is very limited. Fewer than 30 cases have been reported, and in most of them the Melody valve (Medtronic, Inc., Minneapolis, MN, USA) was used. With this case report and review of literature we sought to evaluate the safety and feasibility of the Edwards SAPIEN transcatheter valve (Edwards Lifesciences, Irvine, CA, USA) in valve implantation in the tricuspid position and to compare this intervention with the more established Melody valve implantation. METHODS AND RESULTS We describe one of the rarely reported Edwards SAPIEN valve implantations in a bioprosthetic tricuspid valve which is also the first in a patient with Ebsteins anomaly. A review is presented of all eight case reports on Edwards SAPIEN valve implantations in tricuspid position. The procedure was successful in all cases. Valve performance after implantation was good and no complications were described. In only one procedure pre-stenting was performed. Transatrial, transjugular and transfemoral approaches have been used. The results are comparable to those of the series about Melody valve-in-valve implantation in the tricuspid valve. Mid-term follow-up data are not yet available for both valves. CONCLUSIONS Edwards SAPIEN valve implantation in tricuspid bioprosthetic valves is feasible and safe. Considering the available sizes of the Edwards SAPIEN valve, it may become the preferred prosthesis for valve-in-valve implantation in the tricuspid position in the future.

Acute anti-ischemic effects of perindoprilat in men with coronary artery disease and their relation with left ventricular function

Long-term angiotensin-converting enzyme (ACE) inhibition may reduce ischemic events in patients with coronary artery disease, but whether it protects against acute ischemia or the effects of preexisting left ventricular (LV) dysfunction on potential anti-ischemic properties is unknown. We performed a double-blind trial in 25 patients with exercise-induced ischemia. The effects of perindoprilat on pacing-induced myocardial ischemia were examined. Fourteen patients received perindoprilat and 11 patients received placebo. Based on LV function, 2 subgroups were formed in the perindoprilat group: 7 patients with LV dysfunction (LV ejection fraction <0.40), and 7 patients with normal LV function. After receiving the study medication, the pacing test was repeated. During the first pacing test both groups developed ischemia. After perindoprilat administration, the increase in systemic vascular resistance and LV end-diastolic pressure were significantly blunted (p <0.05). Further, the ischemia-induced increase in arterial and cardiac uptake of norepinephrine was inhibited by perindoprilat, and the increase in atrial natriuretic peptide was less pronounced; also, ST-segment depression was reduced by 32% compared with placebo (all p <0.05). In the group with LV dysfunction, perindoprilat reduced LV end-diastolic pressure significantly by 67% and myocardial lactate production was prevented, but this did not happen in the group with normal LV function. In addition, the increase in arterial norepinephrine was reduced by 74% and 33%, respectively (p <0.05). These results indicate that perindoprilat reduced acute, pacing-induced ischemia in normotensive patients. In patients with (asymptomatic) LV dysfunction these effects were more pronounced than in patients with normal LV function.

Clinical correlates of arterial lactate levels in patients with ST-segment elevation myocardial infarction at admission: a descriptive study

IntroductionBlood lactate measurements can be used as an indicator of hemodynamic impairment and relate to mortality in various forms of shock. Little is known at the moment concerning the clinical correlates of systemic lactate in patients with ST-segment elevation myocardial infarction (STEMI).MethodsTo assess the relation of systemic arterial lactate levels in STEMI patients with clinical correlates at presentation in the catheterization laboratory, we measured arterial lactate levels with a rapid point-of-care technique, immediately following femoral sheath insertion. The study population (n= 1,176) was divided into tertiles with lactate levels ≤1.1 (n = 410), 1.2 to 1.7 (n = 398) and ≥1.8 mmol/l (n = 368). We compared both baseline characteristics and outcome measures of the three lactate groups.ResultsFactors independently associated with higher lactate levels were hypotension, heart rate, thrombolysis in myocardial infarction (TIMI) flow 0 to 1, diabetes and non-smoking. Mortality at 30 days in the three groups was 2.0%, 1.5% and 6.5%. The latter group also showed lower blush grades and greater enzymatic infarct sizes. An intra aortic balloon pump (IABP) was used more frequently in patients with higher lactate levels (4.2%, 7.6% and 14.7%).ConclusionsIn STEMI patients, impaired hemodynamics, worse TIMI flow and non-smoking were related to increased arterial lactate levels. Higher lactate levels were independently related with 30-day mortality and an overall worse response to percutaneous coronary intervention (PCI). In particular, acute mortality was related to admission lactates ≥1.8 mmol/L. Point-of-care measurement of arterial lactate at admission in patients with STEMI has the potential to improve acute risk stratification.

Rationale and design of POPular-TAVI: antiPlatelet therapy fOr Patients undergoing Transcatheter Aortic Valve Implantation

BACKGROUND Despite improving experience and techniques, ischemic and bleeding complications after transcatheter aortic valve implantation (TAVI) remain prevalent and impair survival. Current guidelines recommend the temporary addition of clopidogrel in the initial period after TAVI to prevent thromboembolic events. However, explorative studies suggest that this is associated with a higher rate of major bleeding without a decrease in thromboembolic complications. METHODS The POPular TAVI trial is a prospective randomized, controlled, open-label multicenter clinical trial to test the hypothesis that monotherapy with aspirin or oral anticoagulation (OAC) after TAVI is safer than the addition of clopidogrel for 3 months, without compromising clinical benefit. This trial encompasses 2 cohorts: cohort A, patients are randomized 1:1 to aspirin vs aspirin + clopidogrel, and cohort B, patients on OAC therapy are randomized 1:1 to OAC vs OAC + clopidogrel. Primary outcome is freedom from non-procedure-related bleeding at 1 year. Secondary net-clinical benefit outcome is freedom from the composite of cardiovascular death, non-procedural-related bleeding, myocardial infarction, or stroke at 1 year. The primary outcome is analyzed for superiority, whereas the secondary outcome is analyzed for noninferiority. Recruitment began in February 2014, and the trial will continue until a total of 1,000 patients (684 expected in cohort A and 316 in cohort B) are included and followed up for 1 year. SUMMARY The POPular TAVI trial (NCT02247128) is the first large randomized controlled trial to test if monotherapy with aspirin or OAC vs additional clopidogrel after TAVI reduces bleeding with a favorable net-clinical benefit.