Gerrit Veen

Improved clinical outcome after invasive management of patients with recent myocardial infarction and proven myocardial viability: primary results of a randomized controlled trial (VIAMI-trial)

BackgroundPatients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA).MethodsPatients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded.ResultsThe primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051).ConclusionWe demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability.Trial registrationClinicalTrials.gov: NCT00149591.

Turning 18 with congenital heart disease: prediction of infective endocarditis based on a large population

AIMSnThe risk of infective endocarditis (IE) in adults with congenital heart disease is known to be increased, yet empirical risk estimates are lacking. We sought to predict the occurrence of IE in patients with congenital heart disease at the transition from childhood into adulthood.nnnMETHODS AND RESULTSnWe identified patients from the CONCOR national registry for adults with congenital heart disease. Potential predictors included patient characteristics, and complications and interventions in childhood. The outcome measure was the occurrence of IE up to the age of 40 and 60. A prediction model was derived using the Cox proportional hazards model and bootstrapping techniques. The model was transformed into a clinically applicable risk score. Of 10 210 patients, 233 (2.3%) developed adult-onset IE during 220 688 patient-years. Predictors of IE were gender, main congenital heart defect, multiple heart defects, and three types of complications in childhood. Up to the age of 40, patients with a low predicted risk (<3%) had an observed incidence of less than 1%; those with a high predicted risk (≥3%) had an observed incidence of 6%. The model also yielded accurate predictions up to the age of 60.nnnCONCLUSIONnAmong young adult patients with congenital heart disease, the use of six simple clinical parameters can accurately predict patients at relatively low or high risk of IE. After confirmation in other cohorts, application of the prediction model may lead to individually tailored medical surveillance and educational counselling, thus averting IE or enabling timely detection in adult patients with congenital heart disease.

Relation between exercise-induced hypertension and sustained hypertension in adult patients after successful repair of aortic coarctation.

Objectives To investigate whether exercise-induced hypertension in successfully repaired adult post-coarctectomy patients is associated with hypertension on 24-h blood pressure measurement and increased left ventricular mass. Methods One hundred and forty-four consecutive post-coarctectomy patients (mean age 31.5 years, range 17–74 years; mean age at repair 7.9 years, range 0–45 years) from three tertiary referral centres were studied using ambulatory blood pressure monitoring, treadmill exercise testing and echocardiography. Results Of the 144 patients, 27 (19%) were known to have sustained hypertension, based on their history, and all were on antihypertensive medication. However, 32 (27%) of the remaining 117 patients showed elevated mean daytime systolic blood pressure readings at 24-h ambulatory blood pressure monitoring (systolic blood pressure ⩾ 140 mmHg). Of the remaining 85 patients with normal mean daytime systolic blood pressure, 18 patients (21%) had exercise-induced hypertension (maximal exercise systolic blood pressure > 200 mmHg). Mean daytime systolic blood pressure was higher in the exercise-induced hypertensive patients compared to the normotensive patients with normal exercise blood pressure (134 ± 5 versus 129 ± 7 mmHg, P = 0.008). By multivariate analysis, both maximal exercise systolic blood pressure (P = 0.007) and resting systolic blood pressure (P < 0.0001) were independently associated with mean daytime systolic blood pressure. Maximal exercise systolic blood pressure had no independent predictive value for left ventricular mass (P = 0.132). Conclusions In adult post-coarctectomy patients, maximal exercise systolic blood pressure is independently associated with mean daytime systolic blood pressure at ambulatory blood pressure monitoring. In this study no independent predictive value of maximal exercise systolic blood pressure for left ventricular mass could be demonstrated.

ULTRASOUND ENHANCED PREHOSPITAL THROMBOLYSIS USING MICROBUBBLES INFUSION IN PATIENTS WITH ACUTE ST ELEVATION MYOCARDIAL INFARCTION: PILOT OF THE SONOLYSIS STUDY

In animal studies, transthoracic ultrasound and microbubbles have shown to dissolve thrombi in ST elevation myocardial infarction (STEMI). To examine this effect in patients, we have initiated the Sonolysis trial. In this pilot study of 10 patients with a first acute STEMI, we investigated the safety and feasibility of this trial. After pretreatment in the ambulance, five patients were randomized to receive microbubbles with three-dimensional (3-D) guided high mechanical index impulses (1.18) for 15 min, whereas the control group received placebo without ultrasound. Subsequently, primary percutaneous coronary intervention (PPCI) was performed, if indicated. All patients successfully underwent study treatment and PPCI. No significant difference between treatment and control group in safety (minor adverse events 2/5 vs. 2/5, p = NS) and outcome (TIMI III flow 3/5 vs. 1/5 respectively, p = 0.23) was recorded. These results demonstrate that the study protocol is feasible in the acute cardiac care setting and safe during treatment and follow-up.

The smoker's paradox after successful fibrinolysis: reduced risk of reocclusion but no improved long-term cardiac outcome

Background In smokers treated with fibrinolysis for ST-elevation myocardial infarction (STEMI) a paradoxical beneficial short-term outcome has been reported. This was attributed to favorable clinical and angiographic baseline variables and a better response to fibrinolysis. During follow-up infarct artery reocclusion is an important prognosticator. We studied the effects of smoking on reocclusion and long-term cardiac outcome after successful fibrinolysis. Methods In the Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis trials (APRICOT-1 and -2) 499 STEMI patients with an open infarct artery <48xa0h after fibrinolysis received randomized antithrombotic treatment until 3-month follow-up angiography. Five-year clinical follow-up was complete. Results Current smokers (317 patients, 64%) had favorable clinical (age 54 vs. 60xa0years, Pxa0<xa00.01) and angiographic (single vessel disease 61% vs. 49%, Pxa0=xa00.02) baseline characteristics. Reocclusion rates were 21% (67/317) in smokers versus 32% (59/182) in non-smokers (Pxa0<xa00.01). Five-year infarct-free cardiac survival did not differ: 82% vs. 85%. Reocclusion (HR 2.41, 95%CI 1.05–5.56, Pxa0=xa00.04) independently predicted cardiac mortality. Smoking was independently associated with a reduced risk of reocclusion (OR 0.58, 95%CI 0.37–0.91, Pxa0=xa00.02), but not with improved 5-year cardiac outcome (HR 1.34, 95%CI 0.79–2.25, Pxa0=xa0ns). Conclusions After successful fibrinolysis, smoking is independently associated with a more than 40% reduced risk of reocclusion, which is an independent predictor of adverse outcome. However, even with more favorable baseline characteristics smokers did not have improved 5-year cardiac outcome in this low-risk population.

Early and long-term outcome of elective stenting of the infarct-related artery in patients with viability in the infarct-area: Rationale and design of the Viability-guided Angioplasty after acute Myocardial Infarction-trial (The VIAMI-trial)

BackgroundAlthough percutaneous coronary intervention (PCI) is becoming the standard therapy in ST-segment elevation myocardial infarction (STEMI), to date most patients, even in developed countries, are reperfused with intravenous thrombolysis or do not receive a reperfusion therapy at all. In the post-lysis period these patients are at high risk for recurrent ischemic events. Early identification of these patients is mandatory as this subgroup could possibly benefit from an angioplasty of the infarct-related artery.Since viability seems to be related to ischemic adverse events, we initiated a clinical trial to investigate the benefits of PCI with stenting of the infarct-related artery in patients with viability detected early after acute myocardial infarction.MethodsThe VIAMI-study is designed as a prospective, multicenter, randomized, controlled clinical trial. Patients who are hospitalized with an acute myocardial infarction and who did not have primary or rescue PCI, undergo viability testing by low-dose dobutamine echocardiography (LDDE) within 3 days of admission. Consequently, patients with demonstrated viability are randomized to an invasive or conservative strategy. In the invasive strategy patients undergo coronary angiography with the intention to perform PCI with stenting of the infarct-related coronary artery and concomitant use of abciximab. In the conservative group an ischemia-guided approach is adopted (standard optimal care).The primary end point is the composite of death from any cause, reinfarction and unstable angina during a follow-up period of three years.ConclusionThe primary objective of the VIAMI-trial is to demonstrate that angioplasty of the infarct-related coronary artery with stenting and concomitant use of abciximab results in a clinically important risk reduction of future cardiac events in patients with viability in the infarct-area, detected early after myocardial infarction.

Left ventricular remodeling after acute myocardial infarction: the influence of viability and revascularization - an echocardiographic substudy of the VIAMI-trial

BackgroundViability seems to be important in preventing ventricular remodeling after acute myocardial infarction (AMI). We investigated the influence of viability, as demonstrated with low-dose dobutamine echocardiography, and the role of early revascularization on the process of left ventricular (LV) remodeling after AMI.MethodsWe retrospectively investigated 224 patients who were initially included in the viability-guided angioplasty after acute myocardial infarction-trial (VIAMI-trial). Patients in the VIAMI-trial did not undergo a primary or rescue percutaneous coronary intervention and were stable in the early in-hospital phase. Patients underwent viability testing within 72xa0hours after AMI. Patients with viability were randomized to an invasive strategy or an ischemia-guided strategy. Follow-up echocardiography was performed at a mean of 205xa0days. In this echocardiographic substudy, patients were divided into three new groups: group 1, viable and revascularized before follow-up echocardiogram; group 2, viable, but medically treated; and group 3, non-viable patients.ResultsGroup 1 showed preservation of LV volume indices. The ejection fraction (EF) increased significantly from 54.0% to 57.5% (Pu2009=u20090.047). Group 2 showed a significant increase in LV volume indices with no improvement in EF (53.3% versus 53.0%, Pu2009=u20090.86). Group 3 showed a significant increase in LV volume indices, with a decrease in EF from 53.5% to 49.1% (Pu2009=u20090.043). Multivariate logistic regression analysis indicated the number of viable segments and revascularization during follow-up as independent predictors for EF improvement, especially in patients with lower EF at baseline.ConclusionViability early after AMI is associated with improvement in LV function after revascularization. When viable myocardium is not revascularized, the LV tends to remodel with increased LV volumes, without improvement of EF. Absence of viability results in ventricular dilatation and deterioration of EF, irrespective of revascularization status.Trial registrationNCT00149591 (assigned: 6 September 2005).

Long-term follow-up of the viability guided angioplasty after acute myocardial infarction (VIAMI) trial

BACKGROUNDnPatients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia. In non-high risk patients, with proven viability in the infarct-area, the VIAMI trial showed benefit of early in-hospital stenting of the infarct-related coronary artery for the composite of death, myocardial infarction (MI), or unstable angina (UA) at 1 year follow-up. In this study we evaluated the long-term outcome (median 8 years) of patients included in the VIAMI-trial.nnnMETHODSnAfter being stable during the first 48 h of their acute MI, we randomly assigned 216 patients with viability to an invasive (PCI) or a conservative (ischemia-guided) strategy. The primary outcome was the composite endpoint of death from any cause, recurrent myocardial infarction, or unstable angina. The secondary outcome of this study was the need for (repeat) revascularization.nnnRESULTSnThe combined endpoint of death, recurrent MI and UA was 20.8% in the invasive group and 32.7% in the conservative group (hazard ratio 0.59; 95% CI 0.36-0.99, p = 0.049). No differences were seen in death (8.5% vs. 8.2%, p = 0.80) or MI (7.5% vs. 10.9%, p = 0.48). Only UA showed a significant difference (4.7% vs. 13.6%, p = 0.002). Repeated revascularization was performed in 22.6% of the invasive group and 41.8% of the conservative group (hazard ratio 0.43; 95% CI 0.29-0.74, p < 0.001).`nnnCONCLUSIONnIn patients with acute MI (treated with thrombolysis or without reperfusion therapy) and proven viability in the infarct-area, we demonstrated a long-term benefit of early in-hospital stenting of the infarct-related coronary artery.

Sustained coronary patency after fibrinolytic therapy as independent predictor of 10-year cardiac survival: Observations from the Antithrombotics in the Prevention of Reocclusion in COronary Thrombolysis (APRICOT) trial

BACKGROUNDnWhether late coronary patency after myocardial infarction has prognostic impact independent of left ventricular function remains a matter of debate. Reocclusion rates in the first year after fibrinolysis vary between 20% and 30%. Of all reocclusions, about 30% present as clinical reinfarction, associated with a 2-fold-increased risk of mortality. The clinical impact of reocclusion that presents without reinfarction has not been studied; but an association has been demonstrated with impaired contractile recovery of left ventricular function, the strongest prognosticator of long-term outcome. We therefore studied the impact of 3-month coronary patency after successful fibrinolysis on 10-year cardiac survival.nnnMETHODSnIn the APRICOT-1 trial, 248 ST-elevation myocardial infarction patients with an open infarct artery 24 hours after fibrinolysis had 3-month repeated angiography. Ten-year clinical follow-up was complete in 99.6%.nnnRESULTSnThe reocclusion rate was 29% (71/248). Of these reocclusions, 24% presented as clinical reinfarction (17/71). Cardiac survival at 10 years was 73% in patients with a reoccluded infarct artery and 88% in patients with sustained patency (P < .01). This difference was also present in patients in whom reocclusion was only detected as a result of systematic repeated angiography, that is, in the absence of reinfarction or ischemic symptoms between angiograms (70% vs 86%, P < .03). Multivariable analysis identified sustained patency at 3-month angiography as independent predictor of 10-year cardiac survival (hazard ratio 2.10, 95% CI 1.10-4.02) together with left ventricular ejection fraction.nnnCONCLUSIONSnSustained infarct artery patency in the first 3 months after successful fibrinolysis is a strong predictor of 10-year cardiac survival, independent of left ventricular function. Notably, this also holds true when reocclusion occurs without signs of clinical reinfarction or recurrent ischemia. Therefore, future preventive strategies should also focus on clinically silent reocclusions. Additional studies on better antithrombotic regimens and the combination with a routine invasive strategy early after successful fibrinolysis are warranted.

Rationale and design of a trial on the effect of high dose statins on cardiovascular risk in adults after successful coarctation repair

BACKGROUNDnHMG-coA-reductase-inhibitors (statins) have been proven to reduce atherosclerosis progression as observed by carotid intima-media thickness in patients with known coronary heart disease, independent of lipid lowering. Cardiovascular complications are common in patients after successful coarctation repair. The effect of statins on cardiovascular risk in adults after successful coarctation repair has not yet been established.nnnMETHODSnWe designed a multicentre, prospective, randomised, open label trial to evaluate the effect of the HMGcoA-reductase-inhibitor (Atorvastatin) on atherosclerotic progression in adult post-coarctectomy patients. The primary endpoint in this study is the carotid intima-media thickness as measured by Bmode ultrasonography of the carotid arteries.nnnCONCLUSIONnThis large prospective, randomised, open label trial will establish the effect of HMG-coA-reductase inhibitors (Atorvastatin) on cardiovascular risk in adult patients after successful coarctation repair.